Background and Objectives Drug-eluting stents has been used to treat in patients with coronary artery diseases and shown to reduce rate of restenosis. We compared the efficacy and safety of the sirolimus-eluting stent (SES) versus the zotarolimus-eluting stent (ZES) versus the paclitaxel-eluting stent (PES) in patients with acute coronary syndromes. Methods A postspective, multicenter, randomized trial was conducted to evaluate the safety and efficacy of SES (n=2357), ZES (n=283) and PES (n=1771) in 4423 patients undergoing primary percutaneous revascularization. The primary end point was composite of major adverse cardiac events at 6 months and 12 months: all-cause death, cardiac death, myocardial infarction and clinically driven target vessel revascularization. Results At 6 months, the primary endpoint had occurred in a lower patients treated with SES than ZES (8.7% vs. 17%, HR 0.46, 95% CI 0.33-0.65, p<0.001), SES than PES (8.7% vs. 11.3%, HR 0.74, 95% CI 0.60-0.91, p=0.006) and higher patients treated with ZES than PES (17% vs. 11.3%, HR 1.61, 95% CI 1.14-2.25, p=0.005). At 12 months follow-up, this difference was similar results. SES vs. ZES (11.9% vs. 21.4%, HR 0.49, 95% CI 0.36-0.67, p<0.001), SES vs. PES (11.9% vs. 14.8%, HR 0.78, 95% CI���0.65-0.93, p=0.007), ZES vs. PES (21.4% vs. 14.8%, HR 1.57, 95% CI 1.15-2.13, p=0.004). All cause-motality at 12 months was SES vs. ZES (2.7% vs. 6.5%, HR 0.40, 95% CI 0.23-0.68, p<0.001), SES vs. PES (6.5% vs. 3.8%, HR 1.75, 95% CI 1.03-2.97, p=0.03), ZES vs. PES (2.7% vs. 3.8%, HR 0.71, 95% CI 0.50-1.00, p=0.53). Conclusion Compared with ZES and PES, SES had superior clinical outcome.