OBJECTIVES: To characterize patient reported health-related quality of life (HRQoL) measures among migraine prophylaxis users and non-users in the USA, Germany, France, and Japan. METHODS: Data were drawn from the 2014 Adelphi Migraine Disease Specific Program, a cross sectional survey of physicians and their consulting migraine patients across the USA, France, Germany and Japan. Using physicians as the clustering unit, multivariable linear regression examined factors associated with HRQoL (Migraine Disability Assessment scale - MIDAS; EuroQoL 5 Dimension – EQ-5D), controlling for demographic characteristics, prophylaxis use, monthly headache days (HD: 0-3, 4-7, 8-14, ≥15);  migraine-specific acute medications (ACM: 0, 1, >1); time since migraine diagnosis; anxiety; depression; body mass index, over-the-counter medication use; physician specialty; and country. RESULTS: Of 1,972 patients with complete MIDAS scores, 61% were prophylaxis non-users. Mean (SD) MIDAS scores for patients with 4-7, 8-14, and ≥15 HD were: 10.7 (16.5), 16.0 (16.5), and 24.8 (41.6) among prophylaxis non-users and 11.8 (17.1), 17.1 (19.8), and 44.1 (41.1) in prophylaxis users, respectively. Mean (SD) EQ-5D scores for patients with 4-7, 8-14, and ≥15 HD were: 0.90 (0.14), 0.85 (0.20), 0.81 (0.19) in prophylaxis non-users and 0.88 (0.15), 0.83 (0.15), and 0.70 (0.27) among prophylaxis users, respectively. Higher MIDAS scores were significantly associated with: higher HD, prophylaxis users (β=7.51), >1 ACM (β=7.35), neurologists vs primary-care physicians (β=8.11), and females (β=3.46). Lower EQ-5D scores were associated with HD ≥8 (8-14, β=-0.06, and ≥15, β=-0.17), number of comorbidities (β=-0.02), anxiety (β=-0.04), depression (β=-0.05). German patients (vs. U.S) reported higher EQ-5D scores (β=0.08). CONCLUSIONS: These cross-sectional results may be confounded by severe patients being more likely to use migraine therapies. However, the analysis highlights a persistence of substantial burden of migraine disability and HRQoL impairments in patients using prophylaxis. This underscores the need for better therapies to reduce migraine disability and improve HRQoL.