BACKGROUND Brain lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS), but their clinical relevance remains unclear. OBJECTIVES This study sought to investigate whether periprocedural ischemic DWI lesions after CAS or carotid endarterectomy (CEA) are associated with an increased risk of recurrent cerebrovascular events. METHODS In the magnetic resonance imaging (MRI) substudy of ICSS (International Carotid Stenting Study), 231 patients with symptomatic carotid stenosis were randomized to undergo CAS (n = 124) or CEA (n = 107). MRIs were performed 1 to 7 days before and 1 to 3 days after treatment. The primary outcome event was stroke or transient ischemic attack in any territory occurring between the post-treatment MRI and the end of follow-up. Time to occurrence of the primary outcome event was compared between patients with (DWI+) and without (DWI-) new DWI lesions on the post-treatment scan in the CAS and CEA groups separately. RESULTS Median time of follow-up was 4.1 years (interquartile range: 3.0 to 5.2). In the CAS group, recurrent stroke or transient ischemic attack occurred more often among DWI+ patients (12 of 62) than among DWI- patients (6 of 62), with a cumulative 5-year incidence of 22.8% (standard error [SE]: 7.1%) and 8.8% (SE: 3.8%), respectively (unadjusted hazard ratio: 2.85; 95% confidence interval: 1.05 to 7.72; p = 0.04). In DWI+ and DWI- patients, 8 and 2 events, respectively, occurred within 6 months after treatment. In the CEA group, there was no difference in recurrent cerebrovascular events between DWI+ and DWI- patients. CONCLUSIONS Ischemic brain lesions discovered on DWI after CAS seem to be a marker of increased risk for recurrent cerebrovascular events. Patients with periprocedural DWI lesions might benefit from more aggressive and prolonged antiplatelet therapy after CAS. (A Randomised Comparison of the Risks, Benefits and Cost Effectiveness of Primary Carotid Stenting With Carotid Endarterectomy: International Carotid Stenting Study; ISRCTN25337470) (C) 2015 by the American College of Cardiology Foundation.