Background: Limited information is available on long-term outcomes for patients with unprotected left main coronary artery (LMCA) disease who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods and Results: In the MAIN-COMPARE registry 1217 consecutive patients were divided into 353 receiving only bare-metal stents (BMS) and 864 receiving at least 1 DES. The 3-year outcomes were compared using the propensity-score matching and the inverse-probability-of-treatment-weighted (IPTW) method. Patients receiving DES were older and had a higher prevalence of diabetes mellitus, hypertension, hyperlipidemia, and multivessel disease. Comparisons of the two groups using unadjusted log-rank test are shown in the Figure. In 253 propensity-matched pairs of overall population, the 3-year risk of death or MI was similar with use of DES compared with BMS (hazard ratio [HR], 0.783; 95% confidence interval [CI], 0.496-1.235; p=0.2928). However, the risk of target lesion revascularization (TLR) was significantly lower with use of DES than BMS (HR, 0.188; 95% CI, 0.074-0.479; p=0.0005). After adjustment using the IPTW, there remained a significantly lower risk of TLR (HR, 0.379; 95% CI, 0.203-0.708; p=0.0023) and a similar risk of death or MI (HR, 0.881; 95% CI, 0.508-1.529; p=0.6526) with use of DES. Conclusions: Compared with BMS, DES reduces the need for repeat revascularization, without increasing the risk of death or MI for patients with unprotected LMCA stenosis.