There is limited data comparing effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). We compared the long-term outcomes of the 2 revascularization strategies in 1,246 patients presented with NSTE-ACS for left main or multivessel coronary artery disease. Data were pooled from the Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease (BEST) trial, the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease (PRECOMBAT) trial, and the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. The primary outcome was a composite of death from any causes, myocardial infarction, or stroke. The baseline characteristics were similar between the 2 study groups. During the median follow-up of 60 months, the rate of the primary outcome was significantly lower with CABG than with PCI (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56 to 0.98; p = 0.036). This difference was mainly attributed to a significant reduction in the rate of myocardial infarction (HR 0.50; 95% CI 0.31 to 0.82, p = 0.006). The superiority of CABG over PCI was consistent across the major subgroups. The individual risks of death from any causes or stroke were not different between the 2 groups. In contrast, the rate of repeat revascularization was significantly lower in the CABG group than in the PCI group (HR 0.56; 95% CI 0.41 to 0.75, p <0.001). In this study, among patients with NSTE-ACS for left main or multivessel coronary artery disease, CABG significantly reduces the risk of death from any causes, myocardial infarction, or stroke compared with PCI with drug-eluting stents.