Background - Implantation of drug-eluting stents (DES) limits the rate of coronary restenosis in most patients with coronary artery disease, but data are scarce with regard to their use in patients with ST-segment-elevation myocardial infarction and in connection with distal protection of the microvascular perfusion during primary percutaneous coronary intervention. Methods and Results - We randomly assigned 626 patients referred within 12 hours from symptom onset of an ST-elevation myocardial infarction to have a DES or a bare metal stent implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Quantitative coronary angiography was performed during the index treatment and 8 months later. The primary end point was loss of the lumen diameter in the infarct-related lesion induced by neointimal proliferation. Patients were comparable with regard to baseline demographic and angiographic characteristics. The mean late lumen loss was significantly lower in patients treated with a DES (0.06 mm; SD, 0.66 mm) than in patients who had a bare metal stent implanted (0.47 mm; SD, 0.69 mm; P<0.001). The rate of the composite end point of cardiac death, recurrent myocardial infarction, and target lesion revascularization was 8.6% in the DES group versus 14.4% in the bare metal stent group (P=0.03). Cardiac death occurred in 4.2% and 1.6% of the patients (P=0.09) and stent thrombosis occurred in 2.0% and 2.6% (P=0.72), respectively. Conclusion - Implantation of DES improves the angiographic outcome and need for repeat revascularization without increasing the short-term risk of stent thrombosis but has a tendency to increase cardiac death in patients with ST-segment-elevation myocardial infarction.