Background: The application of percutaneous coronary intervention (PCI) to multivessel disease (MVD) has been limited by restenosis which developed in 20% to 25% in the bare metal stent (BMS) era. The development of drug-eluting stents (DES) has demonstrated superiority over BMS in reducing restenosis. We instigated a study to compare the clinical outcome of the DES over coronary artery bypass graft surgery (CABG) in patients with MVD. Methods: Nine hundred eighty-five patients with MVD underwent PCI with DES (n=529) and CABG (n=456), in a single center, between March 2003 and March 2005. Survival analysis was performed for the population who completed 30day (N=980, 99.5%) or 12 month (N=945, 95.9%) clinical follow-up. The primary objective of this study was defined as the absence of major adverse cardiac and cerebral events (MACCE) at 12 month, including death from any cause, cerebrovascular accident (CVA), acute myocardial infarction (AMI), and repeat revascularization by PCI or CABG. The secondary objectives was MACCE at 30 days and to compare the two groups with respect to composite death, AMI, and CVA. Results: The 30 days clinical outcomes were similar between the DES group and the CABG group (0.4 % vs. 0.9%, p = 0.168). During 12 months follow up, the rate of mortality was not significantly different between the two groups (1.9% vs. 2.7%, p = 0.211). The rate of composite death, cerebrovascular accident, myocardial infarction was not significantly different in both groups (2.7% vs. 3.4%, p = 0.269). The cumulative MACCE-free survival was 86.8% in the DES group and 96.2% in the CABG group (p < 0.001). Conclusion: The rate of serious cardiovascular events, which includes death from any cause, CVA, and AMI were no significant difference between the two groups However, despite DES was introduced, overall MACCE was still significantly higher in patients with MVD compared with the CABG. group, determined by the decreased rate of repeat revascularization.