<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2018-05-02</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001609550</issuerCik>
        <issuerName>Inspire Medical Systems, Inc.</issuerName>
        <issuerTradingSymbol>INSP</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001055951</rptOwnerCik>
            <rptOwnerName>ORBIMED ADVISORS LLC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>601 LEXINGTON AVENUE, 54TH FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>NEW YORK</rptOwnerCity>
            <rptOwnerState>NY</rptOwnerState>
            <rptOwnerZipCode>10022</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001615374</rptOwnerCik>
            <rptOwnerName>OrbiMed Capital GP V LLC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>601 LEXINGTON AVENUE, 54TH FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>NEW YORK</rptOwnerCity>
            <rptOwnerState>NY</rptOwnerState>
            <rptOwnerZipCode>10022</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Series E Convertible Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F1"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>1582904</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F4"/>
                    <footnoteId id="F5"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Series F Convertible Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F3"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F1"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>548817</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F4"/>
                    <footnoteId id="F5"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Shares of Series E and Series F Convertible Preferred Stock (collectively, the &quot;Convertible Preferred Stock&quot;) have no expiration date and are convertible, at the option of the holder, into shares of Common Stock at the then-effective conversion rate for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Issuer's Sixth Amended and Restated Certificate of Incorporation (as amended, the &quot;Certificate of Incorporation&quot;)).  The shares of Convertible Preferred Stock will automatically convert into shares of Common Stock at the then-effective conversion rate for no additional consideration (subject to the payment of cash in lieu of any fractional shares in accordance with the Certificate of Incorporation) immediately prior to the closing of the Issuer's initial public offering.</footnote>
        <footnote id="F2">Shares of Series E Convertible Preferred Stock are convertible into shares of Common Stock at a 1-for-0.1728 conversion rate.</footnote>
        <footnote id="F3">Shares of Series F Convertible Preferred Stock are convertible into shares of Common Stock at a 1-for-0.1504 conversion rate.</footnote>
        <footnote id="F4">These shares of Series E and Series F Convertible Preferred Stock are held of record by OrbiMed Private Investments V, LP (&quot;OPI V&quot;).  OrbiMed Capital GP V LLC (&quot;GP V&quot;) is the sole general partner of OPI V, and OrbiMed Advisors LLC (&quot;Advisors&quot;), a registered adviser under the Investment Advisers Act of 1940, as amended, is the sole managing member of GP V.  By virtue of such relationships, GP V and Advisors may be deemed to have voting and investment power with respect to the securities held by OPI V noted above and as a result may be deemed to have beneficial ownership over such securities.  Advisors exercised this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the Shares held by OPI V.</footnote>
        <footnote id="F5">Each of GP V and Advisors disclaims beneficial ownership of the securities reported herein for purposes of Rule 16a-1(a) under the Securities Exchange Act of 1934, as amended (the &quot;Exchange Act&quot;), except to the extent of its interest therein, if any.  This report shall not be deemed an admission that any such entity is a beneficial owner of such securities for the purpose of Section 16 of the Exchange Act, or for any other purpose.</footnote>
    </footnotes>

    <remarks>Exhibit List: Exhibit 24 - Power of Attorney</remarks>

    <ownerSignature>
        <signatureName>/s/ Richard Buchholz, Attorney-in-Fact for OrbiMed Advisors LLC</signatureName>
        <signatureDate>2018-05-02</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Richard Buchholz, Attorney-in-Fact for OrbiMed Capital GP V LLC</signatureName>
        <signatureDate>2018-05-02</signatureDate>
    </ownerSignature>
</ownershipDocument>
