Background: There were no published data regarding the long-term clinical efficacy and safety of second generation drug-eluting stent (zotarolimus-eluting stents, ZES) following primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). Methods: This study was aimed to establish the clinical outcomes of PCI with ZES compared to first generation DES (sirolimus-eluting stent, SES and paclitaxel-eluting stent, PES) for primary PCI in STEMI. A prospective, open-labeled, randomized multi-center trial has been performed at 11 centers in Korea. All patients will be clinically followed-up for two years. The primary endpoint was major adverse cardiac event (MACE): the composite of cardiac death (CD), recurrent MI and ischemia-driven target lesion revascularization (TLR)) at two years. Stent thromboses (ST) by ARC definition were analyzed. Results: Total 485 patients (ZES=164, SES=160, PES=160) who were completed more than two year were analyzed. Two-year MACE were 6.1%, 2.5% and 4.4% in ZES-, SES- and PES-group, respectively (p=0.278). ST was two (1.2%), four (2.5%) and three (1.9%) in ZES-, SES- and PES- group, respectively (p=0.7). Nine month angiographic follow up was completed in 50.3%. Late loss was 0.65 짹 0.64 mm, 0.12 짹 0.39 mm and 0.35 짹 0.58 mm in ZES-, SES- and PES- group (p<0.001). Predictors of MACE were old age (>75 years), diabetes, late loss and baseline heart rate at the time of enrollment but not affected by stent differences. Conclusions: Campared to SES and PES, ZES were not different in terms of MACE and ST through two-year clinical follow-up in patients following primary PCI.