Background: Drug-eluting stent implantation significantly improved the angiographic and long-term clinical outcomes compared with bare-metal stent implantation in diabetic patients, mainly driven by reduced target lesion revascularization. However, comparison of long-term clinical outcomes between sirolimus-eluting stent (SES) with paclitaxel-eluting stent (PES) in diabetic patients has not been sufficiently evaluated. Methods: This prospective, multicenter, randomized study compared SES (n=200) and PES implantation (n=200) for diabetic patients (n=400). We compared the long-term clinical outcomes (death, myocardial infarction, and target lesion revascularization) between two groups. Results: The 2 groups had similar baseline clinical and angiographic characteristics. Six-month angiographic restenosis (4.0% vs. 20.8%, p<0.001), 9-month target lesion revascularization (2.0% vs. 7.5%, p=0.017), and major adverse cardiac events (2.0% vs. 8.0%, p=0.010) including death, myocardial infarction, and target lesion revascularization were significantly lower in SES versus PES group. At 2 years, there was no difference in the incidence of death (0% vs. 1.5%, p=0.248) and myocardial infarction (0.5% vs. 1.0%, p=0.999). However, the target lesion revascularization (3.5% vs. 11.0%, p=0.004) and major adverse cardiac events (3.5% vs. 12.5%, p=0.001) were significantly lower in SES versus PES group. Two stent thromboses (1 acute, 1 very late) occurred in the SES group during dual antiplatelet therapy and none in the PES group. Conclusions: SES implantation is superior to reducing 2-year target lesion revascularization and improving 2-year clinical outcomes in patients with diabetes mellitus and coronary artery disease compared to PES implantation.