This study was aimed to evaluate outcomes of patients with unprotected left main coronary artery (LMCA) stenosis who were treated with drug-eluting stents. Sixty-three consecutive patients with unprotected LMCA stenosis were treated with sirolimus-eluting stents in 52 (83%) patients and paclitaxel-eluting stents in 11 (17%) patients, in whom percutaneous intervention was considered the sole alternative because of high surgical risk and/or patient preference. Urgent percutaneous coronary intervention within 24 hours after angiography was performed in 6 (10%) patients. The patients were predominantly at high surgical risk with 35 (56%) having EuroSCORE >6 and 39 (62%) having Parsonnet score >15. Involvement of the distal LMCA was observed in 46 (73%) patients. Procedural success was achieved in all patients. Intravascular ultrasound was used in 51 (81%) patients. Single-stenting strategy was adopted in 36 (78%) patients with bifurcation stenosis. There were no death, Q-wave myocardial infarction, stent thrombosis, or urgent repeat revascularization events during hospitalization. Over a mean follow-up of 11.7 +/- 7.7 months, 18 (29%) patients experienced major adverse cardiac events, including 3 (5%) deaths, 7 (11%) myocardial infarctions, and 10 (16%) target lesion revascularizations. Stent thrombosis developed in 1 (0.6%) patient at 35 days after the procedure. Bifurcation involvement was an independent predictor of major adverse cardiac events by multivariate analysis (hazard ratio 12.90, 95% confidence interval 1.36 to 122.45, p = 0.0259). In conclusion, drug-eluting stent placement for unprotected LMCA stenosis may be a feasible therapeutic alternative in patients at high surgical risk. However, bifurcation stenosis remains a significant predictor of unfavorable clinical outcome.