It is unknown whether the effect of diabetes on patients with unprotected left main coronary artery (LMCA) disease differs according to the different revascularization strategies. This study was conducted to evaluate the impact of diabetes on patients with unprotected LMCA disease treated with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). We prospectively enrolled 823 consecutive patients with unprotected LMCA disease who had drug-eluting stent (DES; n = 331) implantation or underwent CABG (n = 492) in the study. We compared the effects of diabetes on clinical outcomes according to different revascularization strategies. Among 823 eligible patients enrolled, 226 had diabetes. In the DES population, no significant differences were observed in occurrences of death, cardiac death, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events. However, the risks of the composite of death/myocardial infarction (MI)/stroke (21.5 % DM vs. 7.2 % non-DM; p = 0.001) and MI (15.4 % DM vs. 1.6 % non-DM; p = 0.000) were significantly higher in the diabetic patients than those without diabetes. In the CABG population, similar rates of all clinical endpoints were observed between the diabetic and nondiabetic group. Diabetes was associated with worse outcome in patients undergoing DES implantation for the treatment of unprotected LMCA disease. However, its negative prognostic impact was not found among patients undergoing CABG.