Antiplatelet therapy with aspirin and clopidogrel is standard care following revascularization by percutaneous coronary intervention with stent insertion. This so-called dual therapy is recommended for up to 4 weeks after intervention for bare-metal stents and for 6-12 months after intervention for drug-eluting stents. Although it is estimated that 5% of patients undergoing percutaneous coronary intervention require long-term anticoagulation because of an underlying chronic medical condition, continuing treatment with triple therapy (warfarin, aspirin and clopidogrel) increases the risk of bleeding. In most patients triple antithrombotic therapy seems justified for a short period of time. In some patients, however, a more considered judgment based on absolute need for triple therapy, risk of bleeding and risk of stent thrombosis is required, but the optimum antithrombotic treatment for these patients who require long-term anticoagulation has not been defined. This Review summarizes the existing literature concerning antithrombotic therapy and makes recommendations for initiation and duration of triple therapy in the small proportion of patients already receiving anticoagulant therapy who require percutaneous coronary intervention.