Background: Long-term outcomes of drug-eluting stent implantation for unprotected left main coronary artery (ULMCA) stenosis have not been determined. Methods: The long-term clinical outcomes of 293 consecutive patients with de novo ULMCA lesions treated with DES were compared with historical controls, consisting of 199 patients treated with bare-metal stents. Follow-up duration was truncated to 2 years to compare the events of death, myocardial infarction , target vessel revascularization, any stent thrombosis and composites of adverse events. Hazard ratios (HR) using the Cox model were adjusted by propensity score quintiles and established risk factors. Results: Of the patients, 279 (95.2%) received sirolimus-eluting stents and 14 (4.8%) received paclitaxel-eluting stents. DES patients had more extensive coronary artery stenosis and bifurcation ULMCA lesions, and received more complex stenting procedures. The outcomes and HRs of the overall population are presented in the table. The incidence of any stent thrombosis did not differ between DES and BMS patients (0.8% vs. 2.1%, p=0.1937). DES patients had a lower risk of target vessel revascularization, both in bifurcation (9.0% vs. 23.3%; adjusted HR, 0.23; 95% CI, 0.09-0.59; p=0.0021) and non-bifurcation (6.4% vs. 17.1%; adjusted HR, 0.31; 95% CI, 0.09-1.03; p=0.0561) lesions. Conclusions: Use of DES for ULMCA stenosis was associated with a lower incidence of repeat revascularization while maintaining comparable incidences of death, myocardial infarction, and stent thrombosis over 2-years, irrespective of lesion location.