This study was performed to compare the safety and efficacy of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) on the outcomes of diabetic patients. Recent data with drug-eluting stents have shown improved clinical outcomes in diabetic patients. This study compared outcomes between the 2 available drug-eluting stents, SESs and PESs. From the prospective drug-eluting stent registries at the investigators' institution, 1,320 consecutive diabetic patients treated with SESs (n=873, 1,293 lesions) and PESs (n=447, 733 lesions) were identified and their in-hospital and 1- and 6-month clinical outcomes compared. Baseline characteristics showed more men, more patients with previous coronary bypass surgery, and smaller ejection fractions in the PES group and more obese patients in the SES group. Procedural characteristics were similar except for more left anterior descending artery and proximal lesions and the greater use of glycoprotein IIb/IIIa inhibitors in the SES group and more type C lesions, direct stenting, and stents per patient in the PES group. In-hospital complications were similar. Clinical follow-up at 1 month was also similar between the 2 groups, including subacute stent thrombosis. At 6 months, the 2 groups had similar mortality (7% vs 7%), myocardial infarctions (18% vs 21%), target lesion revascularization, target vessel revascularization, major adverse cardiac events (11% vs 12%), and late thrombosis (0.3% vs 0%). Subanalysis of insulin-treated diabetic patients showed no significant differences in outcomes in the 2 groups. No significant differences were found between SESs and PESs on Cox regression analysis for hazard ratios. In conclusion, SESs and PESs are associated with similar efficacy and safety with regard to repeat revascularization rates, major adverse cardiac events, and stent thrombosis up to 6 months for the treatment of coronary artery disease in patients with diabetes mellitus regardless of insulin therapy.