OBJECTIVE: Drug-eluting stents (DES) have become the principal coronary artery revascularization modality in the US; yet little is known about their long-term clinical outcomes versus bare-metal stents (BMS). We examined 2-year clinical event rates for BMS vs. DES in a practice-based population and compared results for patients with single- as well as multi-vessel coronary artery disease (CAD). METHODS: The study population includes Duke University Medical Center patients undergoing revascularization with BMS or DES between January 1, 2000 and May 31, 2005, with follow-up through August 17, 2006. Study outcomes examined are death, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR), and their composites. RESULTS: We examined the data of 3678 BMS and 1689 DES patients. DES vs. BMS patients had more multi-vessel CAD (42.6% vs. 36.6%). At two years follow-up, DES vs. BMS patients had lower rates of mortality (7.8% vs. 8.6%), non-fatal MI (3.3% vs. 5.0%), and TVR (6.0% vs. 14.2%). This difference in DES vs. BMS TVR rate was observed in patients with 1- (5.5% vs. 13.0%), 2- (6.7% vs. 15.7%), and 3-vessel CAD (7.0% vs. 18.8%). After adjustment for differences in baseline characteristics using Cox proportional hazards modeling, DES vs. BMS use was associated with no difference in mortality; but with significant reductions in the composites of death or MI (HR = 0.81, 95% CI = 0.67, 0.98) and death, MI, or TVR (HR = 0.55, 95% CI = 0.47, 0.64). Event reduction in the adjusted models was not limited to 1-, 2-, or 3-vessel CAD patients. CONCLUSIONS: The use of drug-eluting vs. bare-metal stents is associated with significant improvements in long-term clinical outcomes for patients with single- and multi-vessel coronary artery disease.