- Objectives We sought to compare patient-oriented outcomes related to target vessel or nontarget vessel events for sirolimus-eluting stents (SES) versus bare-metal stents. Background SES significantly reduce restenosis but the influence of reduced restenosis on overall patient-oriented outcome has not been reported. Methods The study population included 1,057 patients randomized in the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) study and followed clinically for 5 years. The primary end point was a composite of all-cause mortality, any myocardial infarction, or any repeat revascularization. In secondary analyses, myocardial infarction and repeat revascularization events attributed to the target vessel or a nontarget vessel were compared by stent type. Results Patients with an SES were more likely to be free from the primary composite end point at 5 years (60.4% vs. 47.8%, p < 0.001) chiefly due to a sustained reduction in target lesion revascularization for SES (cumulative incidence: 12.5% vs. 28.8%, p < 0.001). There was no difference in the cumulative incidence of myocardial infarction or revascularization attributed to remote segments of the target vessel. Events attributed to the nontarget vessel were frequent and not different for SES versus bare-metal stents (25.7% vs. 25.8%). Conclusions The benefit of SES over bare-metal stents for reduced target lesion revascularization is maintained for 5 years. Remote coronary segments of the target vessel and nontarget vessel remain an important cause of future adverse events despite sustained restenosis benefit.