Drug-eluting stents (DES) have been shown to markedly reduce the need for repeat revascularization compared to bare-metal stents in patients with stable coronary artery disease. The benefit of DES in patients with acute coronary syndromes (ACS) is unclear. This analysis was undertaken to determine if DES have similar advantages over bare-metal stents in patients with ACS. A cohort of 3,771 patients underwent percutaneous coronary intervention with stent implantation in native coronary arteries. Patients presenting for primary angioplasty or rescue angioplasty were excluded. Patients were classified as having stable or unstable symptoms on presentation and then further divided by stent type, DES or bare-metal stent. Although there was a difference in efficacy, with fewer major adverse cardiac events after DES implantation for the stable patients at 1 year (8.2% vs 13.2%, p = 0.008), this benefit was not found in patients with ACS (11.2% vs 12.0%, p = 0.6). A reduced need for repeat revascularization of the initially treated artery accounted for this difference (5.6% vs 11.4%, p <0.001). Stent thrombosis by 1 year was equally rare with each stent type. In conclusion, the reduction in the need for repeat revascularization associated with DES appears to be limited to patients who present with stable angina pectoris. This observation may reflect the more frequent presence of vulnerable plaques in patients with ACS.