Objectives: The aim of this study is to compare the clinical outcomes of ZES and SES in real- world patients with ST-segment elevation acute myocardial infarction (STEMI). Background: Zotarolimus-eluting stents (ZES) showed higher in-segment late luminal loss and in-segment binary restenosis rate compared with sirolimus eluting stents (SES) in several studies. However, no data are available on direct comparison of the clinical outcomes between two stents in unselected patients with ST-segment elevation acute myocardial infarction. Methods: 873 patients with STEMI (306 patients in ZES group, 567 patients in SES group) were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) between Jan 2007 and Jan 2008. Primary end points were major adverse cardiac events (MACE), a composite of all cause of death, myocardial infarction, target lesion revascularization during 12-month clinical follow-up. Results: During one-year follow up, the primary end points occurred in 140 patients (16.0%). Use of glycoprotein IIb/IIIa inhibitor and multi-vessel disease were more common in the SES group. SES group, however, had significantly lower incidences of MACE [Hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.07-2.16, p=0.02], target lesion revascularization (HR 2.16, 95% CI 1.01-4.59, p=0.046) and target vessel revascularization (HR 2.24, 95% CI 1.18-4.24, p=0.013), but not death or MI (HR 1.37, 95% CI 0.91-2.05, p=0.129). Conclusions: SES implantation showed better one-year clinical outcomes in patients with STEMI compared with ZES implantation, mainly by reducing angiographic restenosis.