BACKGROUND A major concern with carotid artery stenting (CAS) is the potential for cerebral embolism. The purpose of this study was to determine whether virtual histology intravascular ultrasound (VH-IVUS) can predict the risk of a silent ischemic lesion after CAS. METHODS We performed CAS in 45 patients with carotid stenosis. Before CAS, we assessed plaque characteristics by VH-IVUS. We also performed diffusion-weighted magnetic resonance imaging of the brain before and after CAS to detect newly appearing ipsilateral silent ischemic lesions (NISIL). RESULTS In the patient group that was positive for NISIL (P group: n = 18), the relative fibrofatty (FF) area identified by VH-IVUS in 5 cross-sections including the most stenotic lesion was significantly larger than that in areas of the NISIL-negative group (N group: n = 27; 32.7 ± 13.2 and 18.3 ± 9.8%, respectively; p < 0.001). The relative fibrous area was significantly lower in the P group than in the N group (59.2 ± 9.5 and 74.6 ± 9.1%, respectively; p < 0.001). There were no differences in the relative dense calcium and necrotic core areas between the P and N groups. From the analysis of receiver operating characteristic curves, most reliable cutoff values for predicting NISIL were a relative FF area of 30% in the most stenotic lesion. In multivariate logistic regression analysis, the relative FF area was an independent predictor of NISIL (p = 0.005). CONCLUSIONS Quantitative tissue characterization of atherosclerotic lesions of carotid arteries using VH-IVUS was useful to predict NISIL after CAS. However, the positive predictive value determined by VH-IVUS was not superior to that determined by a noninvasive method.