Background— The aim of the study was to compare the outcomes after placement of the everolimus-eluting stent (EES; Xience V) and the sirolimus-eluting stent (SES; Cypher) in patients with coronary artery disease. The second-generation EES is currently one of the most commonly used drug-eluting stents in clinical practice. Although it has clearly been shown superior to paclitaxel-eluting stents, its relative merits against SES have been less extensively assessed. Methods and Results— We identified 5 eligible randomized trials comparing EES with SES in 7370 patients. The primary end point was major adverse cardiac events. Secondary end points were cardiac death, myocardial infarction, repeat revascularization, and the composite of definite and probable stent thrombosis. Overall hazard ratios (HR) and 95% confidence intervals (CI) were calculated for EES versus SES for each of the end points. No heterogeneity across the trials was observed regarding the primary and secondary end points. The risk of major adverse cardiac events (HR, 0.91 [95% CI, 0.77 to 1.08]; P =0.28), cardiac death (HR, 1.02 [95% CI, 0.73 to 1.41]; P =0.92), myocardial infarction (HR, 0.97 [95% CI, 0.66 to 1.35]; P =0.76), repeat revascularization (HR, 0.85 [95% CI, 0.68 to 1.07]; P =0.16), and composite of definite and probable stent thrombosis (HR, 0.79 [95% CI, 0.49 to 1.27], P =0.33) were not significantly different between EES and SES. Conclusions— This meta-analysis did not show significant differences between EES and SES in terms of clinical efficacy and safety. Future studies with longer follow-up are needed to better define the relative merits of these drug-eluting stents.