The antiphospholipid syndrome (APS) is a common cause of both arterial and venous thrombosis. While studies exist demonstrating the role of APS in coronary artery bypass graft failure, its role in stent thrombosis is less clearly documented. Also, a literature search of PubMed did not reveal any articles regarding the coexistence of clopidogrel resistance and APS despite increasing awareness of resistance to clopidogrel treatment. We present a case of a 59-year-old male having recurrent myocardial infarction after subacute restenosis of multiple drug-eluting stents despite anticoagulant therapy. The patient had in-stent thrombosis of seven drug-eluting stents in a course of eight days. He was subsequently found to have mild elevation of IgG anticardiolipin (aCL) antibody titers and resistance to clopidogrel. Long-term anticoagulation with a combination of low-molecular-weight heparin, clopidogrel, and aspirin has been effective. While the patient's aCL titer level was not elevated above the level required by the current diagnostic criteria for APS, we believe that this patient suffers from the antiphospholipid syndrome. We will discuss some of the controversies surrounding the diagnosis of APS as well as appropriate treatment and recognition of the coexistence of APS and clopidogrel resistance in patients with stent thrombosis.