<PAGE>

        As filed with the Securities and Exchange Commission on January 31, 2001
                                                   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              (IRS Employer Identification No.)
of incorporation or organization)

                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                                DURHAM, NC 27707
                                 (919) 493-5980
               (Address of principal executive offices) (Zip Code)
                              --------------------
                         TRIANGLE PHARMACEUTICALS, INC.
                            1996 STOCK INCENTIVE PLAN
                            (Full title of the Plans)
                              --------------------
                              DAVID W. BARRY, M.D.
                      CHAIRMAN AND CHIEF EXECUTIVE OFFICER
                         TRIANGLE PHARMACEUTICALS, INC.
                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                                DURHAM, NC 27707
                                 (919) 493-5980

       (Name, address including zip code, and telephone number, including
                        area code, of agent for service)


<PAGE>




<TABLE>
<CAPTION>

                                        CALCULATION OF REGISTRATION FEE
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
                                                      Proposed     Proposed
        Title of                                      Maximum      Maximum
       Securities                 Amount              Offering     Aggregate          Amount of
         to be                    to be                Price        Offering         Registration
       Registered               Registered(1)        per Share(2)   Price(2)             Fee
       ----------               ----------           ------------  ---------         ------------
       <S>                     <C>                   <C>          <C>               <C>
       Common Stock             964,315 shares        $7.00        $6,750,205        $1,690
       $0.001 par value
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------

</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
     January 25, 2001, as reported by the Nasdaq National Market.


<PAGE>

This Registration Statement on Form S-8 (the "Registration Statement") relates
to the registration of an additional 964,315 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) and January 14, 2000 (Registration
No. 333-94725). 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, 1999 are incorporated by reference in
this Registration Statement and have been so incorporated in reliance on the
report of PricewaterhouseCoopers LLP, independent public accountants, given on
the authority of said firm as experts in auditing and accounting.



<PAGE>


                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT


Item 8.   EXHIBITS

      NUMBER    EXHIBIT

      5         Opinion and consent of Brobeck, Phleger & Harrison LLP.
     23.1       Consent of PricewaterhouseCoopers LLP, Independent
                Accountants.
     23.2       Consent of Brobeck, Phleger & Harrison LLP is contained in
                Exhibit 5.
     24         Power of Attorney. Reference is made to pages II-2 and II-3
                of this Registration Statement.


                                         II-1


<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 31st day of January, 2001.

                                  TRIANGLE PHARMACEUTICALS, INC.

                                  By: /s/ David W. Barry
                                     -----------------------------------
                                       David W. Barry
                                       Chairman and Chief Executive Officer and
                                       Director


                                  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
David W. Barry and Chris A. Rallis 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-2

<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.


SIGNATURE                           TITLE                       DATE

/s/ David W. Barry           Chairman and Chief Executive
------------------------     Officer (Principal Executive      January 31, 2001
David W. Barry               Officer)

/s/ Chris A. Rallis          Director, President and
-------------------------    Chief Operating Officer           January 31, 2001
Chris A. Rallis

/s/ Robert F. Amundsen, Jr.  Executive Vice President and
-------------------------    Chief Financial Officer           January 31, 2001
Robert F. Amundsen, Jr.      (Principal Financial and
                             Accounting Officer)

/s/ Anthony B. Evnin
-------------------------    Director                          January 31, 2001
Anthony B. Evnin

/s/ Standish M. Fleming
-------------------------    Director                          January 31, 2001
Standish M. Fleming

/s/ Dennis B. Gillings
-------------------------    Director                          January 31, 2001
Dennis B. Gillings

/s/ Arthur J. Higgins                                          January 31, 2001
-------------------------    Director
Arthur J. Higgins

/s/ George McFadden
-------------------------    Director                          January 31, 2001
George McFadden

/s/ Henry G. Grabowski
-------------------------    Director                          January 31, 2001
Henry G. Grabowski


                                         II-3



<PAGE>

                                    EXHIBIT INDEX

      NUMBER    EXHIBIT

      5         Opinion and consent of Brobeck, Phleger & Harrison LLP.
     23.1       Consent of PricewaterhouseCoopers LLP, Independent
                Accountants.
     23.2       Consent of Brobeck, Phleger & Harrison LLP is contained in
                Exhibit 5.
     24         Power of Attorney. Reference is made to page II-2 of this
                Registration Statement.
[{"type": "S-8", "sequence": "1", "filename": "a2036663zs-8.txt", "description": "S-8", "secsgml_size_bytes": 10367}]
{"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": "333-54696", "film-number": "1520462"}, "business-address": {"street1": "4 UNIVERSITY PLACE", "street2": "4611 UNIVERSITY DRIVE", "city": "DURHAM", "state": "NC", "zip": "27707", "phone": "9194935980"}, "mail-address": {"street1": "4 UNIVERSITY PLACE", "street2": "4611 UNIVERSITY DRIVE", "city": "DURHAM", "state": "NC", "zip": "27707"}}
As filed with the Securities and Exchange Commission on January 31, 2001
                                                   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              (IRS Employer Identification No.)
of incorporation or organization)

                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                                DURHAM, NC 27707
                                 (919) 493-5980
               (Address of principal executive offices) (Zip Code)
                              --------------------
                         TRIANGLE PHARMACEUTICALS, INC.
                            1996 STOCK INCENTIVE PLAN
                            (Full title of the Plans)
                              --------------------
                              DAVID W. BARRY, M.D.
                      CHAIRMAN AND CHIEF EXECUTIVE OFFICER
                         TRIANGLE PHARMACEUTICALS, INC.
                               4 UNIVERSITY PLACE
                              4611 UNIVERSITY DRIVE
                                DURHAM, NC 27707
                                 (919) 493-5980

       (Name, address including zip code, and telephone number, including
                        area code, of agent for service)
CALCULATION OF REGISTRATION FEE
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
                                                      Proposed     Proposed
        Title of                                      Maximum      Maximum
       Securities                 Amount              Offering     Aggregate          Amount of
         to be                    to be                Price        Offering         Registration
       Registered               Registered(1)        per Share(2)   Price(2)             Fee
       ----------               ----------           ------------  ---------         ------------
Common Stock             964,315 shares        $7.00        $6,750,205        $1,690
       $0.001 par value
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
(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
     January 25, 2001, as reported by the Nasdaq National Market.
This Registration Statement on Form S-8 (the "Registration Statement") relates
to the registration of an additional 964,315 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) and January 14, 2000 (Registration
No. 333-94725). 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, 1999 are incorporated by reference in
this Registration Statement and have been so incorporated in reliance on the
report of PricewaterhouseCoopers LLP, independent public accountants, given on
the authority of said firm as experts in auditing and accounting.
PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 8.   EXHIBITS

      NUMBER    EXHIBIT

      5         Opinion and consent of Brobeck, Phleger & Harrison LLP.
     23.1       Consent of PricewaterhouseCoopers LLP, Independent
                Accountants.
     23.2       Consent of Brobeck, Phleger & Harrison LLP is contained in
                Exhibit 5.
     24         Power of Attorney. Reference is made to pages II-2 and II-3
                of this Registration Statement.

                                         II-1
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 31st day of January, 2001.

                                  TRIANGLE PHARMACEUTICALS, INC.

                                  By: /s/ David W. Barry
                                     -----------------------------------
                                       David W. Barry
                                       Chairman and Chief Executive Officer and
                                       Director

                                  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
David W. Barry and Chris A. Rallis 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-2
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                       DATE

/s/ David W. Barry           Chairman and Chief Executive
------------------------     Officer (Principal Executive      January 31, 2001
David W. Barry               Officer)

/s/ Chris A. Rallis          Director, President and
-------------------------    Chief Operating Officer           January 31, 2001
Chris A. Rallis

/s/ Robert F. Amundsen, Jr.  Executive Vice President and
-------------------------    Chief Financial Officer           January 31, 2001
Robert F. Amundsen, Jr.      (Principal Financial and
                             Accounting Officer)

/s/ Anthony B. Evnin
-------------------------    Director                          January 31, 2001
Anthony B. Evnin

/s/ Standish M. Fleming
-------------------------    Director                          January 31, 2001
Standish M. Fleming

/s/ Dennis B. Gillings
-------------------------    Director                          January 31, 2001
Dennis B. Gillings

/s/ Arthur J. Higgins                                          January 31, 2001
-------------------------    Director
Arthur J. Higgins

/s/ George McFadden
-------------------------    Director                          January 31, 2001
George McFadden

/s/ Henry G. Grabowski
-------------------------    Director                          January 31, 2001
Henry G. Grabowski

                                         II-3
EXHIBIT INDEX

      NUMBER    EXHIBIT

      5         Opinion and consent of Brobeck, Phleger & Harrison LLP.
     23.1       Consent of PricewaterhouseCoopers LLP, Independent
                Accountants.
     23.2       Consent of Brobeck, Phleger & Harrison LLP is contained in
                Exhibit 5.
     24         Power of Attorney. Reference is made to page II-2 of this
                Registration Statement.