Background: The PRECOMBAT randomized study showed a non-inferiority of percutaneous coronary intervention (PCI) with the first-generation sirolimus-eluting stent (SES) for unprotected left main coronary artery (ULMCA) stenosis compared with coronary artery bypass graft surgery (CABG) with regard to the incidence of 1-year major adverse cardiac and cerebrovascular events (MACCE) including death, myocardial infarction (MI), stroke or ischemia-driven target vessel revascularization (TVR). However, the efficacy of the second-generation drug-eluting stent for such a lesion is not known well. Method: The PRECOMBAT-2 study prospectively enrolled 397 consecutive patients who received PCI with everolimus-eluting stent (EES) for ULMCA stenosis. From this registry, the outcomes of 334 (84.1%) patients meeting the randomization criteria of the PRECOMBAT study were compared with those of patients randomized to SES (N=327) and CABG (N=272) in the PRECOMBAT study. The primary end point was the rate of MACCE over 2 years. Results: Baseline clinical characteristics were well matched among the 3 groups. However, angiographic follow-up was less frequently performed in the EES than in the SES group due to the less obligatory recommendation (60.8% vs. 76.1%, p<0.001). The MACCE rate over 2 years did not differ significantly among the 3 groups as shown in Figure. The 2-year incidences of composite of death, MI or stroke also did not differ among SES, EES and CABG groups (3.3% vs. 4.4% vs. 4.8%, p among the 3 groups=0.70). However, the incidence of ischemia-driven TVR was lower in the CABG (3.4%) than in the EES (7.2%) or SES (9.2%) groups (p among the 3 groups=0.023). Between the EES and SES groups, the incidences of MACCE and any individual end points were not different over 2 years. Conclusions: EES showed a similar efficacy for the treatment of ULMCA stenosis, as compared with PCI with SES or CABG, with regard to the incidence of MACCE over 2 years.