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To determine whether the assessment of brain white matter lesion (WML) central veins differentiate patients with primary progressive MS (PPMS) from relapsing-remitting MS (RRMS) and ischemic small vessel disease (SVD) using 3T MRI.In this cross-sectional study, 71 patients with PPMS, RRMS, and SVD were imaged using a T2*-weighted sequence. Two blinded raters identified the total number of WMLs, proportion of WMLs in periventricular, deep white matter (DWM) and juxtacortical regions, and proportion of WMLs with central veins in all patient groups. The proportions were compared between disease groups, including effect sizes. MS or SVD was categorized using a threshold of ≥40% WMLs with central veins as indicative of MS. Interrater and intrarater reproducibility was calculated.The mean proportion of WMLs with central veins was 68.4% in PPMS, 74.3% in RRMS, and 4.7% in SVD. The difference in proportions between PPMS and SVD groups was significant (p < 0.0005; effect size: 3.8) but not significant between MS subtypes (p = 0.3; effect size: 0.29). Distribution of WMLs was similar across both MS groups, but despite SVD patients having more DWM lesions than PPMS patients, proportions of WMLs with central veins remained low (2.75% in SVD; 62.5% in PPMS). Interrater and intrarater reproducibility comparing proportions of WMLs with central veins across all patients was 0.86 and 0.90, respectively. Level of agreement between the proportion of WML central veins and established diagnosis was 0.84 and 0.82 for each rater.WML central veins could be used to differentiate PPMS from SVD but not between MS subtypes.