Background This prospective multicenter study compared angiographic in-lesion late lumen loss in de novo native coronary artery lesions (vessel diameter range 2.25-2.75 mm, length range z15 to V30 mm) 8 months after the implantation of a sirolimus-eluting stent with that of similar vessels with the same drug-eluting stent or a bare stent of the SIRIUS study (historical controls). Methods and Results One hundred one patients (study group) were matched and compared with 323 patients receiving the bare stent (bare control group) and with 350 receiving the Cypher stent (Cypher control group) in the SIRIUS trial. Mean in-lesion late loss in the study group was lower than that in the bare control group (0.20 versus 0.76 mm, P b .0001) and not inferior to that in the Cypher control group (0.27 mm, P = .3). Adverse event rates (death and myocardial infarction) were similar between groups. At 8 months, target lesion revascularization rates were 0% in the study group, 13.2% in the bare control group ( P b .001), and 4.6% in the Cypher control group ( P = .03). Conclusions The Cypher Bx Velocity stent was confirmed to be superior to the bare Bx Velocity stent in small coronary vessels in terms of in-lesion late loss 8 months after implantation. (Am Heart J 2006;1511019.e121019.e7.) Rates of angiographic restenosis and target lesion revascularization (TLR) were found to be higher in small vessels (b2.5 mm in diameter) than in larger vessels 6 months after percutaneous transluminal coronary angioplasty or stenting1,2 and 1 year after stenting.3 Predictors of small vessel restenosis are diabetes, complex lesions, and long lesions.1,4,5 Although estenosis has not been conclusively linked to mortality, it can adversely affect quality of life.6 tents reduce restenosis by preventing recoil, but tissue growth renarrows the lumen significantly in approximately 20% of patients.7-12 Small vessel stenting has shown some advantages over balloon angioplasty randomized and nonrandomized trials but a higher risk for restenosis as compared with larger vessels.13-17 In recent years, stents eluting sirolimus or taxol have attenuated vascular hyperproliferation.18-25 Sirolimus prevents neointimal proliferation.26,27 The Cypher (sirolimus-eluting Bx Velocity) stent was compared with the bare Bx Velocity stent in the SIRIUS study...