Background and purposeModifiable lifestyle factors, including diet, have been implicated in multiple sclerosis (MS) progression, but prospective evidence is limited. The aim of this study was to examine prospective relationships between quality of diet and subsequent disability over 7.5 years in an international cohort of people living with MS (pwMS).MethodsData from 602 participants in the HOLISM (Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis) study were analysed. Quality of diet was assessed using the modified Diet Habits Questionnaire (DHQ). Disability was assessed using the Patient‐determined MS Severity Score (P‐MSSS). Characteristics of disability were assessed by log‐binomial, log‐multinomial and linear regression, adjusted for demographic and clinical covariates, as appropriate.ResultsHigher baseline total DHQ scores (>80–89, >89%) were associated with lower risks of increased P‐MSSS at 7.5 years (adjusted risk ratio [aRR] 0.46, 95% confidence interval [CI] 0.23, 0.91 and aRR 0.48, 95% CI 0.26, 0.89, respectively), and with less P‐MSSS accrual (aβ = −0.38, 95% CI −0.78, 0.01 and aβ = −0.44, 95% CI −0.81, −0.06). Of the DHQ domains, fat subscore was most strongly associated with subsequent disability. Participants with reducing baseline‐to‐2.5‐ years total DHQ scores had greater risk of increased P‐MSSS at 7.5 years (aRR 2.77, 95% CI 1.18, 6.53) and higher P‐MSSS accrual (aβ = 0.30, 95% CI 0.01, 0.60). Participants reporting baseline meat and dairy consumption had greater risk of increased P‐MSSS at 7.5 years (aRR 2.06, 95% CI 1.23, 3.45 and aRR 2.02, 95% CI 1.25, 3.25) and higher P‐MSSS accrual (aβ = 0.28, 95% CI 0.02, 0.54 and aβ = 0.43, 95% CI 0.16, 0.69, respectively). However, reported meat consumption was confounded by quality of diet. Changes in meat or dairy consumption from baseline were inconsistently associated with subsequent disability.ConclusionsWe show for the first time robust long‐term associations between quality of diet and subsequent disability progression in pwMS. Subject to replication, dietary modification may represent a point of intervention for reducing disability in pwMS.