<Page>

AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON SEPTEMBER 20, 2002
                                                   REGISTRATION NO.   333-______

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549
                        ---------------------------------
                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933
                                   ----------

                         TRIANGLE PHARMACEUTICALS, INC.
             (Exact name of Registrant as Specified in Its Charter)

                  DELAWARE                               56-1930728
      (State or Other Jurisdiction of                 (I.R.S. Employer
       Incorporation or Organization)                Identification No.)

                                   ----------

                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                          DURHAM, NORTH CAROLINA, 27707
                                 (919) 493-5980
    (Address, Including Zip Code, And Telephone Number, Including Area Code,
                  Of Registrant's Principal Executive Offices)
                                   ----------
                         TRIANGLE PHARMACEUTICALS, INC.
                            1996 STOCK INCENTIVE PLAN
                            (Full Title of the Plans)
                                   ----------
                                 DANIEL G. WELCH
                      CHAIRMAN AND CHIEF EXECUTIVE OFFICER
                         TRIANGLE PHARMACEUTICALS, INC.
                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                          DURHAM, NORTH CAROLINA 27707
                                 (919) 493-5980
    (Name, Address, Including Zip Code, and Telephone Number, Including Area
                           Code, of Agent For Service)
                                   ----------


<Page>

                         CALCULATION OF REGISTRATION FEE

<Table>
<Caption>
                                                      PROPOSED MAXIMUM          PROPOSED MAXIMUM
TITLE OF SECURITIES TO BE       AMOUNT TO BE         OFFERING PRICE PER     AGGREGATE OFFERING PRICE   AMOUNT OF REGISTRATION
        REGISTERED             REGISTERED (1)             SHARE (2)                    (2)                       FEE
-------------------------     ----------------       ------------------     ------------------------   ----------------------
<S>                           <C>                    <C>                    <C>                        <C>
Common Stock, $0.001 par
value per share               3,000,000 shares             $3.52                 $10,560,000                     $972
</Table>


(1) This Registration Statement shall also cover any additional shares of Common
Stock which become issuable under the Triangle Pharmaceuticals, Inc. 1996 Stock
Incentive Plan by reason of any stock dividend, stock split, recapitalization or
other similar transaction effected without Registrant's receipt of consideration
which results in an increase in the number of the outstanding shares of
Registrant's Common Stock.

(2) Calculated solely for purposes of this offering under Rule 457(h) of the
Securities Act of 1933, as amended, on the basis of the average of the high and
low selling prices per share of the Registrant's Common Stock on September 19,
2002, as reported by the Nasdaq National Market.

<Page>

                                     PART II


             INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE

      This Registration Statement on Form S-8 (the "Registration Statement")
relates to the registration of an additional 3,000,000 shares (the "Shares") of
Common Stock, $.001 par value, of the Registrant. The Shares are securities of
the same class and relating to the same employee benefit plan, the Triangle
Pharmaceuticals, Inc. 1996 Stock Incentive Plan, as those shares registered in
the Registrant's Registration Statements on Form S-8, previously filed with the
Securities and Exchange Commission on June 5, 1998 (Registration No. 333-56189),
March 22, 1999 (Registration No. 333-74805), January 14, 2000 (Registration No.
333-94725), January 31, 2001 (Registration No. 333-54696), January 14, 2002
(Registration No. 333-76680) and May 24, 2002 (Registration No. 333-89084). The
earlier Registration Statements on Form S-8 are hereby incorporated by
reference.

      The financial statements contained in the Registrant's Annual Report on
Form 10-K for the year ended December 31, 2001 are incorporated by reference in
this Registration Statement and have been so incorporated in reliance on the
report of PricewaterhouseCoopers LLP, independent accountants, given on the
authority of said firm as experts in auditing and accounting.

The following additional documents are incorporated by reference in this
registration statement:

      1.    Our Quarterly Report on Form 10-Q for the quarterly period
            ended March 31, 2002 filed on May 10, 2002;

      2.    Our Quarterly Report on Form 10-Q for the quarterly period
            ended June 30, 2002 filed on August 13, 2002;

      3.    Our Annual Report on Form 10-K for the fiscal year ended December
            31, 2001 filed on March 25, 2002, including information in our
            Definitive Proxy Statement in connection with our 2002 Annual
            Meeting of Stockholders;

      4.    Our Current Report on Form 8-K filed May 2, 2002, July 31, 2002,
            August 6, 2002, August 13, 2002, August 28, 2002 and September 19,
            2002; and

      5.    The description of our common stock contained in our Registration
            Statements on Form 8-A filed October 18, 1996, February 10, 1999,
            June 18, 1999, August 24, 2001 and July 31, 2002.

      All documents filed by the Company pursuant to Sections 13(a), 13(c), 14
and 15(d) of the Securities and Exchange Act of 1934, as amended (the "Exchange
Act") on or after the date of this Registration Statement and prior to the
filing of a post-effective amendment which

                                     II-1

<Page>

indicates that all securities offered have been sold or which deregisters all
securities then remaining unsold shall be deemed to be incorporated by
reference in this Registration Statement and to be part hereof from the date
of filing of such documents.

ITEM 8.           EXHIBITS

<Table>
<Caption>

      NUMBER      EXHIBIT
      ------      -------
      <S>         <C>
      5           Opinion and consent of Smith, Anderson, Blount, Dorsett,
                  Mitchell & Jernigan, L.L.P.
      23.1        Consent of PricewaterhouseCoopers LLP, Independent
                  Accountants.
      23.2        Consent of Smith, Anderson, Blount, Dorsett, Mitchell &
                  Jernigan, L.L.P. is contained in Exhibit 5.
      24          Power of Attorney.  Reference is made to pages II-3 and
                  II-4 of this Registration Statement.
</Table>

                                     II-2

<Page>

                                   SIGNATURES

      Pursuant to the requirements of the Securities Act of 1933, as amended,
the Registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8, and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Durham, State of North Carolina on this 20th day
of September, 2002.

                                          TRIANGLE PHARMACEUTICALS, INC.

                                          By: /s/ Daniel G. Welch
                                          ----------------------------
                                          Daniel G. Welch
                                          Chairman and Chief Executive
                                          Officer


                                POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS:

      That the undersigned officers and directors of Triangle Pharmaceuticals,
Inc., a Delaware corporation, do hereby constitute and appoint Daniel G. Welch
and R. Andrew Finkle and each one of them, the lawful attorneys-in-fact and
agents with full power and authority to do any and all acts and things and to
execute any and all instruments which said attorneys and agents, and any one of
them, determine may be necessary or advisable or required to enable said
corporation to comply with the Securities Act of 1933, as amended, and any rules
or regulations or requirements of the Securities and Exchange Commission in
connection with this Registration Statement. Without limiting the generality of
the foregoing power and authority, the powers granted include the power and
authority to sign the names of the undersigned officers and directors in the
capacities indicated below to this Registration Statement, to any and all
amendments, both pre-effective and post-effective, and supplements to this
Registration Statement, and to any and all instruments or documents filed as
part of or in conjunction with this Registration Statement or amendments or
supplements thereof, and each of the undersigned hereby ratifies and confirms
all that said attorneys and agents, or any one of them, shall do or cause to be
done by virtue hereof. This Power of Attorney may be signed in several
counterparts.

      IN WITNESS WHEREOF, each of the undersigned has executed this Power of
Attorney as of the date indicated.

                                     II-3

<Page>

      Pursuant to the requirements of the Securities Act of 1933, as amended,
this Registration Statement has been signed below by the following persons in
the capacities and on the dates indicated.


<Table>
<Caption>

         SIGNATURE                               TITLE
         ---------                               -----
<S>                            <C>                                             <C>
/s/ Daniel G. Welch            Chairman of the Board and Chief Executive       September
---------------------------      Officer (Principal Executive Officer)         20, 2002
      Daniel G. Welch

/s/ Chris A. Rallis                        Director, President and             September
---------------------------                Chief Operating Officer             20, 2002
      Chris A. Rallis

/s/ Robert F. Amundsen, Jr.    Executive Vice President and Chief Financial    September
---------------------------     Officer (Principal Financial and Accounting    20, 2002
  Robert F. Amundsen, Jr.                         Officer)

/s/ Anthony B. Evnin                              Director                     September
---------------------------                                                    20, 2002
     Anthony B. Evnin

/s/ Standish M. Fleming                           Director                     September
---------------------------                                                    20, 2002
    Standish M. Fleming

/s/ Dennis B. Gillings                            Director                     September
---------------------------                                                    20, 2002
    Dennis B. Gillings

/s/ Henry G. Grabowski                            Director                     September
---------------------------                                                    20, 2002
    Henry G. Grabowski

/s/ Stewart J. Hen                                Director                     September
---------------------------                                                    20, 2002
      Stewart J. Hen

/s/ Jonathan S. Leff                              Director                     September
---------------------------                                                    20, 2002
     Jonathan S. Leff

/s/ George McFadden                               Director                     September
---------------------------                                                    20, 2002
      George McFadden
</Table>

                                     II-4

<Page>

                                  EXHIBIT INDEX

<Table>
<Caption>

      NUMBER      EXHIBIT
      ------      -------
<S>               <C>
      5           Opinion and consent of Smith, Anderson, Blount, Dorsett,
                  Mitchell & Jernigan, L.L.P.
      23.1        Consent of PricewaterhouseCoopers LLP, Independent
                  Accountants.
      23.2        Consent of Smith, Anderson, Blount, Dorsett, Mitchell &
                  Jernigan, L.L.P. is contained in Exhibit 5.
      24          Power of Attorney.  Reference is made to pages II-3 and
                  II-4 of this Registration Statement.
</Table>
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{"company-data": {"conformed-name": "TRIANGLE PHARMACEUTICALS INC", "cik": "0001022622", "assigned-sic": "2834", "irs-number": "561930728", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-99885", "film-number": "02768627"}, "business-address": {"street1": "4611 UNIVERSITY DRIVE", "city": "DURHAM", "state": "NC", "zip": "27707", "phone": "9194935980"}, "mail-address": {"street1": "4611 UNIVERSITY DRIVE", "city": "DURHAM", "state": "NC", "zip": "27707"}}
AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON SEPTEMBER 20, 2002
                                                   REGISTRATION NO.   333-______

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549
                        ---------------------------------
                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933
                                   ----------

                         TRIANGLE PHARMACEUTICALS, INC.
             (Exact name of Registrant as Specified in Its Charter)

                  DELAWARE                               56-1930728
      (State or Other Jurisdiction of                 (I.R.S. Employer
       Incorporation or Organization)                Identification No.)

                                   ----------

                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                          DURHAM, NORTH CAROLINA, 27707
                                 (919) 493-5980
    (Address, Including Zip Code, And Telephone Number, Including Area Code,
                  Of Registrant's Principal Executive Offices)
                                   ----------
                         TRIANGLE PHARMACEUTICALS, INC.
                            1996 STOCK INCENTIVE PLAN
                            (Full Title of the Plans)
                                   ----------
                                 DANIEL G. WELCH
                      CHAIRMAN AND CHIEF EXECUTIVE OFFICER
                         TRIANGLE PHARMACEUTICALS, INC.
                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                          DURHAM, NORTH CAROLINA 27707
                                 (919) 493-5980
    (Name, Address, Including Zip Code, and Telephone Number, Including Area
                           Code, of Agent For Service)
                                   ----------
CALCULATION OF REGISTRATION FEE
PROPOSED MAXIMUM          PROPOSED MAXIMUM
TITLE OF SECURITIES TO BE       AMOUNT TO BE         OFFERING PRICE PER     AGGREGATE OFFERING PRICE   AMOUNT OF REGISTRATION
        REGISTERED             REGISTERED (1)             SHARE (2)                    (2)                       FEE
-------------------------     ----------------       ------------------     ------------------------   ----------------------
Common Stock, $0.001 par
value per share               3,000,000 shares             $3.52                 $10,560,000                     $972
(1) This Registration Statement shall also cover any additional shares of Common
Stock which become issuable under the Triangle Pharmaceuticals, Inc. 1996 Stock
Incentive Plan by reason of any stock dividend, stock split, recapitalization or
other similar transaction effected without Registrant's receipt of consideration
which results in an increase in the number of the outstanding shares of
Registrant's Common Stock.

(2) Calculated solely for purposes of this offering under Rule 457(h) of the
Securities Act of 1933, as amended, on the basis of the average of the high and
low selling prices per share of the Registrant's Common Stock on September 19,
2002, as reported by the Nasdaq National Market.
PART II

             INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE

      This Registration Statement on Form S-8 (the "Registration Statement")
relates to the registration of an additional 3,000,000 shares (the "Shares") of
Common Stock, $.001 par value, of the Registrant. The Shares are securities of
the same class and relating to the same employee benefit plan, the Triangle
Pharmaceuticals, Inc. 1996 Stock Incentive Plan, as those shares registered in
the Registrant's Registration Statements on Form S-8, previously filed with the
Securities and Exchange Commission on June 5, 1998 (Registration No. 333-56189),
March 22, 1999 (Registration No. 333-74805), January 14, 2000 (Registration No.
333-94725), January 31, 2001 (Registration No. 333-54696), January 14, 2002
(Registration No. 333-76680) and May 24, 2002 (Registration No. 333-89084). The
earlier Registration Statements on Form S-8 are hereby incorporated by
reference.

      The financial statements contained in the Registrant's Annual Report on
Form 10-K for the year ended December 31, 2001 are incorporated by reference in
this Registration Statement and have been so incorporated in reliance on the
report of PricewaterhouseCoopers LLP, independent accountants, given on the
authority of said firm as experts in auditing and accounting.

The following additional documents are incorporated by reference in this
registration statement:

      1.    Our Quarterly Report on Form 10-Q for the quarterly period
            ended March 31, 2002 filed on May 10, 2002;

      2.    Our Quarterly Report on Form 10-Q for the quarterly period
            ended June 30, 2002 filed on August 13, 2002;

      3.    Our Annual Report on Form 10-K for the fiscal year ended December
            31, 2001 filed on March 25, 2002, including information in our
            Definitive Proxy Statement in connection with our 2002 Annual
            Meeting of Stockholders;

      4.    Our Current Report on Form 8-K filed May 2, 2002, July 31, 2002,
            August 6, 2002, August 13, 2002, August 28, 2002 and September 19,
            2002; and

      5.    The description of our common stock contained in our Registration
            Statements on Form 8-A filed October 18, 1996, February 10, 1999,
            June 18, 1999, August 24, 2001 and July 31, 2002.

      All documents filed by the Company pursuant to Sections 13(a), 13(c), 14
and 15(d) of the Securities and Exchange Act of 1934, as amended (the "Exchange
Act") on or after the date of this Registration Statement and prior to the
filing of a post-effective amendment which

                                     II-1
indicates that all securities offered have been sold or which deregisters all
securities then remaining unsold shall be deemed to be incorporated by
reference in this Registration Statement and to be part hereof from the date
of filing of such documents.

ITEM 8.           EXHIBITS
NUMBER      EXHIBIT
      ------      -------
5           Opinion and consent of Smith, Anderson, Blount, Dorsett,
                  Mitchell & Jernigan, L.L.P.
      23.1        Consent of PricewaterhouseCoopers LLP, Independent
                  Accountants.
      23.2        Consent of Smith, Anderson, Blount, Dorsett, Mitchell &
                  Jernigan, L.L.P. is contained in Exhibit 5.
      24          Power of Attorney.  Reference is made to pages II-3 and
                  II-4 of this Registration Statement.
II-2
SIGNATURES

      Pursuant to the requirements of the Securities Act of 1933, as amended,
the Registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8, and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Durham, State of North Carolina on this 20th day
of September, 2002.

                                          TRIANGLE PHARMACEUTICALS, INC.

                                          By: /s/ Daniel G. Welch
                                          ----------------------------
                                          Daniel G. Welch
                                          Chairman and Chief Executive
                                          Officer

                                POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS:

      That the undersigned officers and directors of Triangle Pharmaceuticals,
Inc., a Delaware corporation, do hereby constitute and appoint Daniel G. Welch
and R. Andrew Finkle and each one of them, the lawful attorneys-in-fact and
agents with full power and authority to do any and all acts and things and to
execute any and all instruments which said attorneys and agents, and any one of
them, determine may be necessary or advisable or required to enable said
corporation to comply with the Securities Act of 1933, as amended, and any rules
or regulations or requirements of the Securities and Exchange Commission in
connection with this Registration Statement. Without limiting the generality of
the foregoing power and authority, the powers granted include the power and
authority to sign the names of the undersigned officers and directors in the
capacities indicated below to this Registration Statement, to any and all
amendments, both pre-effective and post-effective, and supplements to this
Registration Statement, and to any and all instruments or documents filed as
part of or in conjunction with this Registration Statement or amendments or
supplements thereof, and each of the undersigned hereby ratifies and confirms
all that said attorneys and agents, or any one of them, shall do or cause to be
done by virtue hereof. This Power of Attorney may be signed in several
counterparts.

      IN WITNESS WHEREOF, each of the undersigned has executed this Power of
Attorney as of the date indicated.

                                     II-3
Pursuant to the requirements of the Securities Act of 1933, as amended,
this Registration Statement has been signed below by the following persons in
the capacities and on the dates indicated.
SIGNATURE                               TITLE
         ---------                               -----
/s/ Daniel G. Welch            Chairman of the Board and Chief Executive       September
---------------------------      Officer (Principal Executive Officer)         20, 2002
      Daniel G. Welch

/s/ Chris A. Rallis                        Director, President and             September
---------------------------                Chief Operating Officer             20, 2002
      Chris A. Rallis

/s/ Robert F. Amundsen, Jr.    Executive Vice President and Chief Financial    September
---------------------------     Officer (Principal Financial and Accounting    20, 2002
  Robert F. Amundsen, Jr.                         Officer)

/s/ Anthony B. Evnin                              Director                     September
---------------------------                                                    20, 2002
     Anthony B. Evnin

/s/ Standish M. Fleming                           Director                     September
---------------------------                                                    20, 2002
    Standish M. Fleming

/s/ Dennis B. Gillings                            Director                     September
---------------------------                                                    20, 2002
    Dennis B. Gillings

/s/ Henry G. Grabowski                            Director                     September
---------------------------                                                    20, 2002
    Henry G. Grabowski

/s/ Stewart J. Hen                                Director                     September
---------------------------                                                    20, 2002
      Stewart J. Hen

/s/ Jonathan S. Leff                              Director                     September
---------------------------                                                    20, 2002
     Jonathan S. Leff

/s/ George McFadden                               Director                     September
---------------------------                                                    20, 2002
      George McFadden
II-4
EXHIBIT INDEX
NUMBER      EXHIBIT
      ------      -------
5           Opinion and consent of Smith, Anderson, Blount, Dorsett,
                  Mitchell & Jernigan, L.L.P.
      23.1        Consent of PricewaterhouseCoopers LLP, Independent
                  Accountants.
      23.2        Consent of Smith, Anderson, Blount, Dorsett, Mitchell &
                  Jernigan, L.L.P. is contained in Exhibit 5.
      24          Power of Attorney.  Reference is made to pages II-3 and
                  II-4 of this Registration Statement.