BACKGROUND The potential benefits and risks of extended use of dual antiplatelet therapy after 12 months in patients receiving drug-eluting stents have not been clearly established. METHODS In two trials, we randomly assigned a total of 2,701 patients who had received drug-eluting stents and were free of major adverse cardiac or cerebrovascular events or major bleeding for at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of cardiac death or myocardial infarction. The trials were merged for analysis. RESULTS The median follow-up was 19.2 months. The cumulative risk of the primary outcome at two years was 1.8% with dual antiplatelet therapy versus 1.2% with aspirin monotherapy (HR, 1.65; 95% CI, 0.80 to 3.36; P=0.17). The individual risks of death, myocardial infarction, stroke, stent thrombosis, repeat revascularization, or major bleeding were not different between the two groups. However, there was a nonsignificant increase in the composite risk of death, myocardial infarction, or stroke (HR, 1.73; 95% CI, 0.99 to 3.0; P=0.051) and in the composite risk of cardiac death, myocardial infarction, or stroke (HR, 1.84; 95% CI, 0.99 to 3.45; P=0.06) in the group that received dual antiplatelet therapy. CONCLUSIONS Extended use of dual antiplatelet therapy beyond 12 months among patients who received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of cardiac death or myocardial infarction. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up.