Background Drug-eluting stents (DES) are increasingly used for treatment of acute ST-elevation myocardial infarction (STEMI), but data comparing outcomes with several DES are limited. Objectives We performed a multicenter, prospectively randomized trial, called the ZEST-AMI trial, to compare the efficacy and safety of the sirolimus- (SES), paclitaxel- (PES) and zotarimus-eluting stent (ZES) in primary intervention for STEMI. Methods and Results The trial included 329 patients at 20 medical centers, who were randomly assigned to SES (n=110), PES (n=111) or ZES (n=108) deployment. The primary end-point was target-vessel failure at 12 months, defined as death, recurrent MI, and target-vessel revascularization. A follow-up angiographic substudy was performed at 8 months after the procedure. The baseline clinical and angiographic characteristics among the groups were well-matched. The mean age was 59 years, and 82% of the patients were men. The prevalence of diabetes mellitus was 23%. The mean reperfusion time was approximately 4 hours. Conclusions The final data will be presented at the meeting.