Pre-procedural white matter changes as a predictive factor for stroke within 30 days of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) was tested in analyzing the International Carotid Stenting Study (ICSS), a multicenter, double-blinded randomized clinical trial treating symptomatic carotid atherosclerosis. 1036 (536 CAS and 500 CEA) randomized patients were enrolled with adequate pre-procedural imaging. The Age-Related White Matter Change (ARWMC) score of 0-30 (3 x 5 regions x 2 hemispheres) was defined by blinded scoring of 5 hemispheric anatomic regions: no lesions (0), focal lesions (1), lesions exceeding 5 mm (2), and territorial involvement (3). Each treatment group was subdivided with ARWMC less than or greater than 7; higher ARWMC scores are hypothesized to correspond to decreased cerebrovascular reserve, parenchymal tolerance of additional ischemic insult, or carotid plaque embolic potential. In the CAS group, an ARWMC of greater than 7 associated with higher overall stroke risk (hazard ratio 2.76 [1.17-6.51] p = 0.021) and non-disabling stroke (hazard ratio 3 [1.1-8.6] p = 0.031). Importantly, high ARWMC CAS group did not carry an increased risk of disabling stroke (final mRS 3 or greater). High ARWMC CEA also did not carry additional stroke risk. Moreover, CAS carried a higher total stroke rate than CEA in high ARWMC patients (HR 2.98, [1.29-6.93]; p = 0.011). ICSS offers the ARWMC score as a useful patient counseling measure for CAS and CEA, even though it is unclear whether white matter lesions are associated with hypertension, hyperlipidemia, active smoking or previous infarct burden, or an independent risk factor. CEA may be preferable in high ARWMC patients.