Although great interest exists in the relative efficacy of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) for the treatment of unprotected left main coronary artery stenosis, data comparing the 2 strategies are scant. Furthermore, no comparison has ever been performed between CABG and drug-eluting stents in this setting. From January 2002 to June 2005, 154 patients with unprotected left main coronary artery stenosis underwent CABG and 157 underwent PCI. Ninety-four patients received a drug-eluting stent in the left main artery. After a median follow-up of 430 days, the rate of mortality, acute myocardial infarction, and target lesion revascularization was 12.3%, 4.5%, and 2.6%, respectively, in the CABG group and 13.4%, 8.3%, and 25.5%, respectively, in the PCI group (death and myocardial infarction p = NS, target lesion revascularization p = 0.0001). Although patients treated with drug-eluting stents had a 25% relative risk reduction in the rate of death, myocardial infarction, and target lesion revascularization compared with patients treated with bare stents, event-free survival was still better for patients treated with CABG. In the multivariate analysis, age >or=70 years, New York Heart Association classes III and IV, acute coronary syndromes, and peripheral vascular disease were the only independent predictors of mortality. In conclusion, our results have indicated that at long-term follow-up no difference exists in the rate of mortality and myocardial infarction between PCI and CABG for the treatment of unprotected left main coronary artery stenosis. However, the rate of target lesion revascularization was higher in the PCI group.