Whether the effect of diabetes on patients with unprotected left main coronary artery (ULMCA) disease differs according to different strategies of revascularization was unknown. This study was conducted to evaluate the impact of diabetes on patients with ULMCA disease treated with either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG). A total of 922 patients with ULMCA disease who received drug-eluting stent (DES) (n = 465) implantation or underwent CABG (n = 457) were retrospectively analyzed. We compared the effects of these 2 treatments on clinical outcomes (death, myocardial infarction, stroke, repeat revascularization, and the composite of death, myocardial infarction, or stroke), according to diabetic status. During the median follow-up of 7.1 years (interquartile range, 5.3 to 8.2 years), no difference was found between PCI and CABG in the adjusted occurrence of death (P = 0.112) and the composite endpoints of death, myocardial infarction, and stroke (P = 0.235). Signifcantly higher incidence of repeat revascularization (P < 0.001) was observed in the DES group, whereas the CABG group had a signifcantly higher rate of stroke (P = 0.001). These trends were consistent in both diabetic and nondiabetic patients. We did not observe signifcant interactions between treatment outcomes and the presence or absence of diabetes after adjustment for covariates (Pinteraction = 0.580 for the composite of death, MI and stroke, Pinteraction = 0.685 for death, Pinteraction = 0.416 for MI, Pinteraction = 0.470 for stroke, and Pinteraction = 0.502 for repeat revascularization). Presence of diabetes was not important for decision-making between CABG and PCI in patients with ULMCA disease. © 2015, International Heart Journal Association. All rights reserved.