This study evaluates the response of the coronary vessel wall to implantation of the sirolimus-eluting stent (SES), Bx-VELOCITY, by using serial intravascular ultrasound. SESs have a major impact on the inhibition of in-stent neointimal hyperplasia. However, changes in the vessel wall and behind stent struts in animal models and humans have not been evaluated after SES implantation. Thirty-four patients who received a SES (n = 24) or a Bx-VELOCITY bare stent (BS) (n = 10) for single de novo coronary lesions and had serial motorized pullback 3-dimensional intravascular ultrasound were included. Stent, lumen, and vessel volumes were similar in the 2 groups at baseline. At follow-up, significantly larger lumen and lower neointimal hyperplasia volumes (0.7 vs 33 mm³, p = 0.001) were seen in the SES group compared with the BS group. There was no significant difference between SES and BS in either the vessel volume (+2.4% vs +0.7%, p = NS) or the plaque behind stent volume change (+3.4% vs +2.5%, p = NS) from after the procedure to late follow-up. The stent edges also showed no significant difference between postprocedural and follow-up measurements, either in patients receiving SESs or BSs. No stented or edge segment required redilatation in the SES group, whereas 2 patients underwent repeat percutaneous coronary angioplasty in the BS group. In the SES group, 1 patient (4%) showed late acquired incomplete stent apposition. Thus, the SES is effective in inhibiting neointimal hyperplasia without affecting vessel volume and plaque behind the stent.