content: <?xml version="1.0" encoding="UTF-8"?><edgarSubmission xmlns="http://www.sec.gov/edgar/ownership" xmlns:com="http://www.sec.gov/edgar/common">
    <headerData>
      <submissionType>144</submissionType>
      <filerInfo>
        <filer>
          <filerCredentials>
            <cik>0001564926</cik>
            <ccc>XXXXXXXX</ccc>
          </filerCredentials>
        </filer>
        <liveTestFlag>LIVE</liveTestFlag>
  
  
      </filerInfo>
    </headerData>
    <formData>
      <issuerInfo>
        <issuerCik>0000874015</issuerCik>
        <issuerName>IONIS PHARMACEUTICALS INC</issuerName>
        <secFileNumber>000-19125</secFileNumber>
        <issuerAddress>
          <com:street1>2855 GAZELLE COURT</com:street1>
          <com:city>CARLSBAD</com:city>
          <com:stateOrCountry>CA</com:stateOrCountry>
          <com:zipCode>92010</com:zipCode>
        </issuerAddress>
        <issuerContactPhone>7609319200</issuerContactPhone>
        <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>O'NEIL PATRICK R.</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
        <relationshipsToIssuer>
          <relationshipToIssuer>Officer</relationshipToIssuer>
        </relationshipsToIssuer>
      </issuerInfo>
      <securitiesInformation>
        <securitiesClassTitle>Common Stock</securitiesClassTitle>
        <brokerOrMarketmakerDetails>
          <name>Morgan Stanley Smith Barney</name>
          <address>
            <com:street1>1585 Broadway</com:street1>
            <com:city>New York</com:city>
            <com:stateOrCountry>NY</com:stateOrCountry>
            <com:zipCode>10036</com:zipCode>
          </address>
        </brokerOrMarketmakerDetails>
        <noOfUnitsSold>7645</noOfUnitsSold>
        <aggregateMarketValue>405185.00</aggregateMarketValue>
        <noOfUnitsOutstanding>143472119</noOfUnitsOutstanding>
        <approxSaleDate>01/17/2024</approxSaleDate>
        <securitiesExchangeName>NASDAQ</securitiesExchangeName>
      </securitiesInformation>
      <securitiesToBeSold>
        <securitiesClassTitle>Common Stock</securitiesClassTitle>
        <acquiredDate>01/16/2024</acquiredDate>
        <natureOfAcquisitionTransaction>RSUs granted under the 2011 Equity Incentive Plan</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Ionis Pharmaceuticals, Inc.</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>7645</amountOfSecuritiesAcquired>
        <paymentDate>01/16/2024</paymentDate>
        <natureOfPayment>Services rendered</natureOfPayment>
      </securitiesToBeSold>
      <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
      <securitiesSoldInPast3Months>
        <sellerDetails>
          <name>Insight Securities, Inc.</name>
          <address>
            <com:street1>600 Central</com:street1>
            <com:street2>STE 293</com:street2>
            <com:city>Highland Park</com:city>
            <com:stateOrCountry>IL</com:stateOrCountry>
            <com:zipCode>60035</com:zipCode>
          </address>
        </sellerDetails>
        <securitiesClassTitle>Common Stock</securitiesClassTitle>
        <saleDate>12/26/2023</saleDate>
        <amountOfSecuritiesSold>20825</amountOfSecuritiesSold>
        <grossProceeds>1072487.50</grossProceeds>
      </securitiesSoldInPast3Months>
      <noticeSignature>
        <noticeDate>01/17/2024</noticeDate>
        <signature>Patrick R. O'Neil</signature>
      </noticeSignature>
    </formData>
  </edgarSubmission>
metadata_documents: [{"type": "144", "sequence": "1", "filename": "primary_doc.xml", "secsgml_size_bytes": 3423}]
text: 144
  0001564926
  XXXXXXXX
  LIVE
  0000874015
  IONIS PHARMACEUTICALS INC
  000-19125
  2855 GAZELLE COURT
  CARLSBAD
  CA
  92010
  7609319200
  O'NEIL PATRICK R.
  Officer
  Common Stock
  Morgan Stanley Smith Barney
  1585 Broadway
  New York
  NY
  10036
  7645
  405185.00
  143472119
  01/17/2024
  NASDAQ
  Common Stock
  01/16/2024
  RSUs granted under the 2011 Equity Incentive Plan
  Ionis Pharmaceuticals, Inc.
  N
  7645
  01/16/2024
  Services rendered
  N
  Insight Securities, Inc.
  600 Central
  STE 293
  Highland Park
  IL
  60035
  Common Stock
  12/26/2023
  20825
  1072487.50
  01/17/2024
  Patrick R. O'Neil