BACKGROUNDWhole brain atrophy is a putative outcome measure in monitoring relapsing‐remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC).METHODSWe studied MS [n = 26, age (mean, range) 43 (21‐55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0‐6.5), timed 25 foot walk (T25FW) 5.95 (3.2‐33.0 seconds)] and NC [n = 9, age 45 (31‐53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3‐dimensional T1‐weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations.RESULTSBPV‐1.5T was higher than BPV‐3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue‐CSF contrast at 3T. BPV‐3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [−74.5 mL (−126.5, −22.5), P = .006, d = .92] when compared to BPV‐1.5T [−51.3.1 mL (−99.8, −2.8), P = .04, d = .67]. Correlations between BPV‐1.5T and EDSS (r = −.43, P = .027) and BPV‐3T and EDSS (r = −.49, P = .011) and between BPV‐1.5T and T25FW (r = −.46, P = .018) and BPV‐3T and T25FW (r = −.56, P = .003) slightly favored 3T. BPV‐cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44‐.58) and 3T (r range = .43‐.53).CONCLUSIONSField strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.