The randomized Reduction of Restenosis In Saphenous Vein Grafts with Cypher Sirolimus-Eluting Stent trial compared angiographic outcomes of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs) in saphenous vein grafts (SVG). Using intravascular ultrasound (IVUS) performed during 6-month follow-up angiography, we compared the vascular effects of the 2 types of stent on SVGs. Of 75 patients (96 lesions) included, 59 patients underwent IVUS in 61 SVGs; 29 patients received 40 SESs for 34 lesions, and 30 patients received 42 BMSs for 39 lesions. IVUS parameters (diameters, areas, and volumes) were compared in the 2 groups. A specific analysis was performed for overlapping SESs. Median neointimal volume was 1.3 mm(3) (interquartile range 0 to 13.1) in SESs versus 24.5 (7.8 to 39.5) in BMSs (p <0.001). Minimal incomplete stent apposition was detected at only 3 stent edges (2 BMSs, 1 SES) next to ectatic regions of the SVG. Compared with single SESs, overlapping SESs showed significant increases in neointimal reaction, with a neointimal volume of 0.6 mm(3)/mm of stent (0.1 to 1.8) versus 0 (0 to 0.4) in single SESs (p = 0.03), and this phenomenon was mainly localized in overlapping SES segments, where neointimal volume per millimeter of stent was 1.1 mm(3)/mm (0.6 to 4.4) versus 0 (0 to 1.3) in nonoverlapping segments (p = 0.05). In conclusion, SESs effectively inhibit neointimal hyperplasia volume compared with BMSs in diseased vein grafts, without evidence of increased incomplete apposition risk. The neointimal response to overlapping SES layers seems higher than to a single SES layer.