OBJECTIVES: Data on psychometric properties of patient-reported outcomes (PROs) in primary progressive multiple sclerosis (PPMS) are lacking. We report the internal consistency and construct validity of the Short Form-36 (SF-36) and the Modified Fatigue Impact Scale (MFIS) at baseline in ORATORIO, a Phase III, randomised, double-blind, placebo-controlled study of ocrelizumab in PPMS. METHODS: SF-36 assesses health-related quality of life across eight subscales; Physical and Mental Component Summary (PCS and MCS) can be calculated, with higher scores indicating better functioning. MFIS assesses effects of fatigue on physical, cognitive and psychosocial functioning, with lower scores indicating less fatigue. Construct validity was determined by calculating the strength of Pearson correlation between the PROs and the clinician-rated Expanded Disability Status Scale (EDSS). Internal consistency was calculated using Cronbach’s α for SF-36 subscales, total MFIS and its subscales (acceptable internal consistency=0.7). The evaluable population included up to 656 patients. RESULTS: PCS, but not MCS, was negatively correlated with EDSS (r=−0.47; p<0.001 and r=−0.06; p=0.16, respectively). MFIS total score was negatively correlated with PCS and MCS (r=−0.50 and −0.53, respectively; both p<0.001) and positively correlated with EDSS (r=0.27; p<0.001). MFIS physical domain was more strongly negatively correlated with PCS than MCS (r=−0.61 and −0.40, respectively; both p<0.001). MFIS cognitive domain was more strongly negatively correlated with MCS than PCS (r=−0.50 and −0.27, respectively; both p<0.001). Internal consistency ranged from 0.69–0.92 (only General Health was <0.7) and from 0.79–0.95 for the SF-36 and MFIS subscales, respectively, and was 0.95 for the total MFIS. CONCLUSIONS: In ORATORIO, PCS and MFIS correlated with the EDSS, stronger correlations existed between more closely related constructs and internal consistency estimates were largely within acceptable ranges. These findings suggest that SF-36 and MFIS are robust measures of functional health and fatigue from the patient’s perspective in PPMS. Sponsored by F. Hoffmann-La Roche Ltd.