The present trial was conducted to evaluate efficacy and safety of sirolimus-eluting stents (SES) in patients with multivessel disease. Six hundred and seven patients were enrolled in the registry in a non-randomized, open-label manner and treated with SES. Patients with left ventricular ejection fraction (LVEF) of < 30%, overt congestive heart failure, history of cerebrovascular accident, transmural myocardial infarction (MI) in previous week, severe hepatic or renal disease, diseased saphenous veins, neutropenia or thrombocytopenia, intolerance or contraindication to aspirin or clopidogrel, or need for major surgery were excluded from the study. Patients were compared to historical controls from the Arterial Revascularization Therapies (ARTS)-1 trial, both coronary artery bypass graft (CABG) surgery (n=602) as well as bare metal stents (BMS) arms (n=600). Few baseline differences were found when comparing patients from present trial with ARTS-1 patients. In ARTS-2, patients were more frequently diabetic (26.2% v. 18.2%) and they more often had 3-vessel disease (54% v. 28%). Lesions were more frequently complex (13.9% v. 7.5% Type C lesions). More stents were implanted per patient than in ARTS-1 BMS (3.7 v. 2.8) group and longer lengths of stent were implanted (73 mm v. 48 mm). Looking at the primary endpoint at 1 year, there was no difference in the incidence of major adverse cardiac and cerebrovascular events (MACCE) comparing the ARTS-2 SES registry patients with the CABG randomized patients in the ARTS-1 trial (10.4% v. 11.6%, p=0.46) but MACCE was lower in ARTS-2 SES compared with BMS patients in ARTS-1 (26.5%). At 1 year, there was no difference in any component of MACCE between the 3 groups: ARTS-2 SES, ARTS-1 BMS and ARTS-1 CABG, respectively as regards death (5% v. 2.7% v. 2.7%), cerebrovascular event (0.8% v. 1.8% v. 1.8%), MI (1.2% v. 5% v. 3.5%) and CABG (2% v. 4.7% v. 7%). The ARTS-1 BMS group was assoicated with a significantly higher rate of revascularization with percutaneous-coronary intervention (PCI) (5.4% v. 12.3% v. 3%). Among patients suitable for either CABG or PCI, this registry experience demonstrates that SES was associated with a low need for repeat revascularization as compared to BMS and had similar MACCE rates as compared to CABG. However, given the registry, non-randomized nature of the study and the comparison with historical controls, conclusions cannot be made about the superiority of one approach over another. The low revascularization rates and clinical adverse events were evident despite the increased length and complexity of lesions treated. Additionally, stent thrombosis was rare (0.8%). Despite attempts to control for confounding variables by using similar inclusion and exclusion criteria between the present registry and the much earlier trial, unidentified modifiers may affect these results. Conclusions regarding superiority of a given therapy would need to be addressed in randomized trials.