OBJECTIVE To define the optimal antiplatelet regime in patients requiring long-term anticoagulation who undergo percutaneous coronary intervention. BACKGROUND Antiplatelet therapy following coronary intervention consists of a regime of aspirin and clopidogrel for the prevention of subacute stent thrombosis. The optimal antiplatelet therapy post-coronary intervention in patients on ongoing anticoagulation therapy remains to be defined. Addition of aspirin and clopidogrel to patients already on warfarin increases the risk of bleeding, while withholding antiplatelet therapy increases the risk of stent thrombosis. Discontinuation of warfarin in turn increases the risk of thromboembolism. METHODS We performed a systematic review and synthesis of the English language literature examining the risk of subacute thrombosis with various antiplatelet regimens and the risk for thromboembolism with and without warfarin. The risk of bleeding complications with various drug combinations were reviewed. CONCLUSIONS There are no data from randomized trials to clarify the optimum treatment in these patients; and the feasibility of such studies may be questionable. Hence, treatment decisions continue to be made on an individualized basis and should include assimilation of information on key factors, including the risk of bleeding and the risk of thromboembolism.