We evaluated the safety and efficacy of dual antiplatelet therapy, in association with oral anticoagulant (OAC) therapy, in patients undergoing percutaneous coronary intervention (PCI). The use of this triple therapy increases the rate of adverse outcomes, as shown by retrospective studies. In this first prospective multicenter registry STENTIng and oral antiCOagulation (STENTICO), all patients with OAC therapy undergoing PCI were included and followed up at 2 and 12 months. A total of 359 patients were included from 40 French centers. In 234 (65.2%; group 1) of these 359 patients, OAC therapy was discontinued (22 +/- 31 days). In 125 patients (34.8%; group 2), triple therapy was continued. The baseline characteristics were similar in the 2 groups. In group 2, a radial approach was more often used (65.6% vs 43.8%, p = 0.003), fewer drug-eluting stents were implanted (33.3% vs 24.8%, p = 0.06), and fewer anti-glycoprotein IIb/IIIa antagonists were prescribed (5.6% vs 8.5%, p = 0.02). The stroke rate did not differ significantly, at 3.0% (95% confidence interval 0.8% to 5.2%) for group 1 versus 0.8% (95% confidence interval -0.8% to 2.4%) in group 2. Severe and moderate bleeding, according to the Global Use of Strategies to Open Coronary Arteries (GUSTO) criteria, occurred in 2.1% and 6.4% of groups 1 and 2, respectively (p = 0.04). A significant difference in bleeding risk was found between the femoral and radial approaches (10.3% vs 3.8%, respectively; p = 0.01). In conclusion, adding dual antiplatelet therapy to pre-existing OAC therapy increases the post-PCI bleeding risk. Temporary discontinuation decreased this bleeding risk but tended to increase the risk of stroke. A radial approach for PCI could be a good alternative to the conventional femoral route to avoid bleeding.