<?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/A</submissionType>
    <previousAccessionNumber>0000874015-24-000094</previousAccessionNumber>
    <filerInfo>
      <filer>
        <filerCredentials>
          <cik>0001537529</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>Monia Brett P</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
      <relationshipsToIssuer>
        <relationshipToIssuer>Officer</relationshipToIssuer>
        <relationshipToIssuer>Director</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>23907</noOfUnitsSold>
      <aggregateMarketValue>1180347.88</aggregateMarketValue>
      <noOfUnitsOutstanding>143472119</noOfUnitsOutstanding>
      <approxSaleDate>02/02/2024</approxSaleDate>
      <securitiesExchangeName>NASDAQ</securitiesExchangeName>
    </securitiesInformation>
    <securitiesToBeSold>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <acquiredDate>02/01/2024</acquiredDate>
      <natureOfAcquisitionTransaction>PSUs grantedunder the 2011Equity IncentivePlan</natureOfAcquisitionTransaction>
      <nameOfPersonfromWhomAcquired>IonisPharmaceuticals, Inc.</nameOfPersonfromWhomAcquired>
      <isGiftTransaction>N</isGiftTransaction>
      <amountOfSecuritiesAcquired>23907</amountOfSecuritiesAcquired>
      <paymentDate>02/01/2024</paymentDate>
      <natureOfPayment>Services rendered</natureOfPayment>
    </securitiesToBeSold>
    <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <name>Insight Securities</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>12/14/2023</saleDate>
      <amountOfSecuritiesSold>24000</amountOfSecuritiesSold>
      <grossProceeds>1190018.00</grossProceeds>
    </securitiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <name>Insite 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>12/20/2023</saleDate>
      <amountOfSecuritiesSold>6500</amountOfSecuritiesSold>
      <grossProceeds>322643.00</grossProceeds>
    </securitiesSoldInPast3Months>
    <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>12/21/2023</saleDate>
      <amountOfSecuritiesSold>17500</amountOfSecuritiesSold>
      <grossProceeds>862577.00</grossProceeds>
    </securitiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <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>
      </sellerDetails>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <saleDate>01/17/2024</saleDate>
      <amountOfSecuritiesSold>32059</amountOfSecuritiesSold>
      <grossProceeds>1620245.83</grossProceeds>
    </securitiesSoldInPast3Months>
    <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>01/25/2024</saleDate>
      <amountOfSecuritiesSold>2285</amountOfSecuritiesSold>
      <grossProceeds>118248.75</grossProceeds>
    </securitiesSoldInPast3Months>
    <remarks>Updated number of shares sold.</remarks>
    <noticeSignature>
      <noticeDate>09/04/2024</noticeDate>
      <signature>Brett P. Monia</signature>
    </noticeSignature>
  </formData>
</edgarSubmission>
