Antiphospholipid syndrome (APS), the most common acquired hypercoagulable condition, is diagnosed by persistent presence of antiphospholipid antibodies and episodes of vascular thrombosis. It may be an important predisposing factor for stent thrombosis, resulting in poor outcomes. Also, anti-platelet therapy non-responsiveness is associated with stent thrombosis. We report a case of a 39-year-old man who after undergoing successful percutaneous coronary intervention for significant coronary artery disease suffered repeated stent thrombosis events leading to ST-segment elevation myocardial infarction. Eventually, he underwent coronary artery bypass surgery because of uncontrolled thrombosis and was diagnosed as having APS and dual antiplatelet therapy non-responsiveness.