We investigated whether severe, MRI-visible perivascular spaces (PVS) in the cerebral hemisphere white matter (centrum semiovale) are more common in patients with pathology-proven cerebral amyloid angiopathy (CAA) than in those with pathology-proven non-CAA-related intracerebral hemorrhage (ICH). Using a validated 4-point scale on axial T2-weighted MRI, we compared PVS in patients with pathology-proven CAA to PVS in those with spontaneous ICH but no histopathologic evidence of CAA. In a preliminary analysis restricted to patients with T2*-weighted gradient-recalled echo MRI, we also investigated whether including severe centrum semiovale PVS increases the sensitivity of existing diagnostic criteria for probable CAA. Fourteen patients with CAA and 10 patients with non-CAA-related ICH were included. Eight of the patients with CAA were admitted for symptomatic, spontaneous lobar ICH, 1 because of ischemic stroke, 1 with transient focal neurologic episodes, and 4 due to cognitive decline. Severe (>20) centrum semiovale PVS were more frequent in patients with CAA compared to controls (12/14 [85.7%; 95% confidence interval (CI): 57.2%-98.2%] vs 0/10 [1-sided 95% CI: 0%-30.8%], p < 0.0005); this was robust to adjustment for age. The original Boston criteria for probable CAA showed a sensitivity of 76.9% (95% CI: 46.2%-95%), which increased to 92.3% (95% CI: 64%-99.8%), without loss of specificity, after including severe centrum semiovale PVS. Severe centrum semiovale PVS on MRI may be a promising new neuroimaging marker for the in vivo diagnosis of CAA. However, our findings are preliminary and require confirmation and external validation in larger cohorts of pathology-proven CAA.