This SIPRI Policy Brief describes European responses to secondary sanctions that the United States imposed on Iran after withdrawing from the 2015 nuclear agreement, or the Joint Comprehensive Plan of Action (JCPOA). In particular, it looks at the Instrument in Support of Trade Exchanges (INSTEX), which was established by France, Germany and the United Kingdom in 2019 to facilitate European–Iranian trade, initially focusing on the humanitarian sector. While falling short of the kind of comprehensive economic normalization that was expected under the JCPOA, INSTEX could help maintain the ailing nuclear agreement in addition to addressing some of the negative humanitarian consequences of sanctions in Iran. INSTEX can also be seen as a test case for a more independent European foreign policy that could better withstand future disagreements with major powers.