Dual antiplatelet treatment with aspirin and a thienopyridine (either ticlopidine or clopidogrel) is currently recommended after percutaneous coronary intervention with stent implantation (PCI-S). This regimen has been proven superior to the combination of oral anticoagulation (OAC) and aspirin, which at present, has therefore little role in this setting. In patients undergoing PCI-S with an indication for long-term OAC, because of atrial fibrillation, mechanical heart valve, previous thromboembolism, etc., the optimal antithrombotic treatment is currently unknown. The limited available evidence shows substantial variability in the management of these patients, who are treated according to standardized protocols only in 54% of cases. The adopted strategies include, either selected or systematic, substitution of OAC for dual antiplatelet therapy in 25 to 54% of cases, addition to OAC of a single antiplatelet agent in 12 to 25% and institution of triple therapy with OAC, aspirin and a thienopyridine in about 60%. OAC is systematically aimed at a lower intensity in 33% of cases only, whereas in another 29% this is pursued when a high hemorrhagic risk is perceived. In 69% of patients having exchanged OAC for dual antiplatelet administration, the original treatment is resumed after 1 to 3-6 months, with longterm association of an antiplatelet agent in most cases. Both efficacy and safety of the various antithrombotic regimens were suboptimal in the small series reported, with a 30-day occurrence of thrombotic and major bleeding complications of 4% and 3 to 7%, respectively. For current practice, stratification of medium-term risk of thrombo-embolism upon OAC interruption is warranted. In low-risk patients (i.e. lone atrial fibrillation, venous thromboembolism > 6 months, etc.), preprocedural OAC interruption and substitution for dual antiplatelet treatment, to be continued for the following 1 to 6 months, is appropriate. In medium- to high-risk patients (i.e. mitral or multiple mechanical valves, recent arterial or venous thromboembolism, etc.), medium-term triple therapy with OAC, aspirin and a thienopyridine should be adopted. In both risk groups, drug-eluting stents should be avoided as much as possible, due to the prolonged need for dual antiplatelet treatment. In the absence of strongly supportive evidence however, large scale registries and clinical trials are warranted to confirm the currently suggested strategies and to evaluate alternative antithrombotic regimens in patients with and indication for OAC undergoing PCI-S, whose number is likely to progressively increase over the next years.