Ezetimibe has been reported to provide significant incremental reduction in low-density-lipoprotein cholesterol (LDL-C) when added to a statin; however, its effect on coronary atherosclerosis has not yet been evaluated in detail. The aim of this study was to investigate the add-on effect of ezetimibe to a statin on coronary atherosclerosis evaluated by intravascular ultrasound (IVUS).In this prospective randomized open-label study, a total of 51 patients with stable coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI) were enrolled, and assigned to a combination group (n = 26, rosuvastatin 5 mg/day + ezetimibe 10 mg/day) or a monotherapy group (n = 25, rosuvastatin 5 mg/day). Volumetric IVUS analyses were performed at baseline and 6 months after the treatment for a non-PCI site. LDL-C level was significantly reduced in the combination group (-55.8%) versus that in the monotherapy group (-36.8%; P = 0.004). The percent change in plaque volume (PV), the primary endpoint, appeared to decrease more effectively in the combination group compared with the monotherapy group (-13.2% versus -3.1%, respectively, P = 0.050). Moreover, there was a significant group × time interaction in the effects of the two treatments on PV (P = 0.021), indicating the regressive effect of the combination therapy on PV was greater than that of monotherapy for subtly different values of baseline PV in the two treatment groups. Moreover, percent change in PV showed positive correlations with percent change of LDL-C (r = 0.384, P = 0.015).Intensive lipid-lowering therapy with ezetimibe added to usual-dose statin may provide significant incremental reduction in coronary plaques compared with usual-dose statin monotherapy.