Objective Virtual histology intravascular ultrasound (VH IVUS) is valuable for estimating minimal lumen diameter and plaque characterization. The clinical use of IVUS in carotid intervention is not well characterized. We aim to evaluate the role of IVUS in carotid plaque characterization and determine whether it could be predictive of procedure-related microemboli. Methods From July 2010, patients with severe carotid stenosis who underwent elective carotid stenting procedures were prospectively enrolled. IVUS evaluation was performed before stent placement. Patient demographics, comorbidities, and preoperative images were recorded. Comparison of pre- and postoperative diffusion-weighted magnetic resonance images was used to identify the number of procedure-related microemboli. IVUS-derived minimal lumen diameter and vessel wall plaque characteristics were collected. Univariate and multivariate logistic regressions were used to search for associations between IVUS-derived VH data and incidence of microemboli. Results A total of 38 high-risk patients receiving carotid stenting were enrolled. Among them, 25 patients had type I aortic arches and 17 of the patients were symptomatic (preoperative stroke or transient ischemic attack). VH IVUS data did not show strong associations with microemboli, however, a trend was found between the area of fibrous tissue and median or more incidence of microemboli (P =.099). IVUS-defined vessel diameter maximum was associated with median or more incidence of microemboli (P =.042). In addition, median or more incidence of microemboli showed trends with proximal common carotid artery calcification (P =.056) and with being over the age of 80 (P =.06). Contralateral carotid occlusion or high-grade stenosis was associated with postoperative contralateral microemboli (P =.036). Conclusions We demonstrate that periprocedural carotid IVUS is clinically feasible. VH IVUS may be helpful in better understanding plaque morphology and determining optimal stent placement. However, its use in predicting microembolization remains limited.