Coronary artery bypass grafting (CABG) has been the recommended treatment for patients with significant left main coronary artery (LMCA) stenosis. Advances in stent technology have invigorated investigations into the suitability of a percutaneous approach for these patients. Favorable short-term results from nonrandomized comparisons were previously reported. Patients (n = 97) who underwent percutaneous coronary intervention for severe (>70%) LMCA stenosis were matched in a 1:2 ratio with a cohort that underwent surgical revascularization (n = 190). The groups were similar for age, gender, European System for Cardiac Operative Risk Evaluation, left ventricular ejection fraction, history of myocardial infarction, and presence of renal disease. Kaplan-Meier estimates of 3-year mortality were similar for the PCI and CABG groups at 80% (95% confidence interval [CI] 68 to 88) versus 85% (95% CI 79 to 89, p = 0.14), respectively. Propensity score-adjusted 3-year mortality did not differ between groups (p = 0.22). Multivariable modeling identified only higher European System for Cardiac Operative Risk Evaluation (hazard rate 1.33, 95% CI 1.16 to 1.54, p <0.001) and the presence of diabetes mellitus (hazard rate 1.96, 95% CI 1.24 to 3.09, p = 0.004) as independent risks of mortality at 3 years. In conclusion, patients who underwent percutaneous revascularization of severe LMCA stenosis appeared to have 3-year survival equivalent to those who underwent CABG. Diabetes mellitus and advanced co-morbidity were the principal determinants of survival. These findings support the need for randomized trials with adequate follow-up to compare the 2 approaches.