Primary percutaneous coronary intervention (PCI) with stent implantation is the preferred method of reperfusion for ST-elevation acute myocardial infarction. Concern remains over the use of drug-eluting stents in the acute ST-elevation myocardial infarction setting, with limited published reports on their use for this application. We studied 64 consecutive patients presenting with an acute ST-elevation myocardial infarction who underwent mechanical reperfusion with implantation of a drug-eluting stent. Both sirolimus- and paclitaxel-eluting stents were used. Primary outcome was the occurrence of major adverse cardiac events, defined as death, nonfatal reinfarction or clinically driven target vessel revascularization. Post-procedural success was achieved in 63 patients (98%). In-hospital mortality was 1.6%. During a median follow-up of 234 days, there were no cases of stent thrombosis, reinfarction or reintervention. These findings conducted in a 'real world' practice setting in the United States demonstrate that drug-eluting stent implantation for acute ST-elevation myocardial infarction is safe and effective, with a low rate of major adverse cardiac events during mid-term follow-up.