Recent data on drug-eluting stents have shown improved clinical outcomes in patients with diabetes mellitus. However, the relative efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) remains controversial. Therefore, a meta-analysis of randomized trials was performed to compare SES with PES exclusively in patients with diabetes. The published research was scanned by formal searches of electronic databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) from January 2001 to April 2009. All randomized trials involving head-to-head comparison of SES versus PES in patients with diabetes were examined for analysis. A total of 5 randomized trials were included in the present meta-analysis, involving 1,173 patients (594 in the SES group, 579 in the PES group). SES were significantly more effective in the reduction of target lesion revascularization (5.1% vs 11.4%, odds ratio [OR] 0.41, 95% confidence interval [CI] 0.26 to 0.64, p <0.001) and angiographic binary (≥50%) restenosis (5.6% vs 16.4%, OR 0.30, 95% CI 0.19 to 0.48, p <0.001) compared to PES. In contrast, the differences between SES and PES were not statistically significant with respect to cardiac death (2.2% vs 2.9%, OR 0.71, 95% CI 0.34 to 1.47, p = 0.35), myocardial infarction (1.5% vs 2.6%, OR 0.58, 95% CI 0.26 to 1.31, p = 0.19), and stent thrombosis (0.6% vs 1.2%, OR 0.57, 95% CI 0.18 to 0.84, p = 0.35). In conclusion, SES are superior to PES in reducing the incidences of restenosis and target lesion revascularization in patients with diabetes, with nonsignificant differences in terms of cardiac death, myocardial infarction, and stent thrombosis.