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Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without the establishment of a formal cause-and-effect relationship between treatment and adverse event. We reported a case of ACS after the first administration of an ICI and with a fatal recurrence in another coronary area immediately after readministration. According to guidelines, causality was considered to be certain. Subsequently, we queried the French pharmacovigilance database and found 4 cases of ACS with coronary artery thrombosis. Causality was probable in those patients. These data suggest that ACS may be another life-threatening cardiac adverse event occurring with ICI exposure.