Background Diabetes mellitus has been shown to be a risk factor for adverse events and a major determinant in selection of a revascularization strategy in patients with multivessel or left main coronary artery (LMCA) disease. We evaluated whether the outcome of drug-eluting stent (DES) treatment and that of coronary artery bypass grafting (CABG) differed in diabetic and nondiabetic patients with unprotected LMCA disease. Methods A total of 1,474 patients with unprotected LMCA stenosis who received DES (n=784) or underwent CABG (n=690) were examined. We compared the effects of these two treatments on long-term clinical outcomes (death; the composite of death, Q-wave myocardial infarction [MI] or stroke; and target vessel revascularization [TVR]), according to diabetic status. Results After adjustment of covariates, the risk of death (hazard ratio [HR], 0.95, 95% confidence interval [CI], 0.62-1.46, p=0.83) and the composite of death, Q-wave MI, or stroke (HR, 0.96, 95% CI, 0.65-1.42, p=0.85) at 3 years were similar in the DES and CABG groups. However, the rate of TVR was significantly higher in the DES group (HR, 4.31, 95% CI, 2.28-8.15, p<0.001). These trends were consistent in both diabetic and non-diabetic patients. We also did not observe a diabetes-associated excess risk of death (pinteraction=0.90 and 0.16), or a composite of death, Q-wave MI, or stroke (pinteraction=0.68 and 0.93), or TVR (pinteraction=0.23 and 0.92), between patients receiving either treatment. Conclusions The prognostic impact of diabetes on long-term treatment with DES or CABG for patients with unprotected LMCA disease was minimal.