In patients undergoing coronary stenting, long-term dual antiplatelet therapy with aspirin and clopidogrel reduces atherothrombotic events but also increases the risk of bleeding. The potential for developing bleeding complications is further enhanced in patients also requiring oral anticoagulant treatment ("triple therapy"). The aim of the study is to assess long-term outcomes associated with the use of triple-therapy in patients undergoing coronary stenting and evaluate how these may be affected by targeting international normalized ratio (INR) values to the lower therapeutic range. We prospectively studied 102 consecutive patients undergoing coronary stenting treated with dual antiplatelet therapy also requiring oral anticoagulation. INR was targeted to the lower therapeutic range (2.0 to 2.5). Patients requiring oral anticoagulant therapy because of mechanical valve prosthesis were excluded. Patients were followed for 18 months, and bleeding, defined according to Thrombolysis in Myocardial Infarction criteria, and major adverse cardiac events were recorded. Outcomes were compared with a control group (n = 102) treated only with dual antiplatelet therapy. The mean duration of triple therapy was 157 +/- 134 days. At 18 months, a nonsignificant increase in bleeding was observed in the triple versus dual therapy group (10.8% vs 4.9%, p = 0.1). INR values were higher in patients with bleeding (2.8 +/- 1.1 vs 2.3 +/- 0.2, p = 0.0001). In patients who had INR values within the recommended target (79.4%), the risk of bleeding was significantly lower compared with patients who did not (4.9 vs 33%, p = 0.00019) and with that observed in the control group (4.9%). An INR >2.6 was the only independent predictor of bleeding. There were no significant differences in major adverse cardiac events between groups (5.8% vs 4.9%, p = 0.7). In conclusion, in patients undergoing coronary stenting on triple therapy, targeting lower therapeutic INR values reduces the risk of bleeding complications.