BACKGROUND: Exercise is a safe and effective way to improve physical function in people with multiple sclerosis (PWMS). OBJECTIVES: This study aimed to perform a head-to-head study of the effects of aerobic and resistance training on physical capacity and physical function. METHODS: A multicentre randomized controlled trial with 150 participants was conducted. Participants were randomized into 12 weeks of either aerobic training (AT; n = 62), resistance training (RT; n = 57), or usual care (UC; n = 31). The primary outcome was physical function (measured as a composite score of the 6-minute walk test and five-time sit-to-stand). Secondary outcomes were aerobic capacity (VO2peak), maximal muscle strength (MVC), and self-reported walking ability. RESULTS: Participants had a mean age of 45.5 (8.8), an expanded disability status scale (EDSS) of 2.8 (1.5), and 75% were female. Physical function did not increase in AT versus UC 0.08 (-0.16 to 0.33) (mean (95% CI)) nor in RT versus UC 0.09 (-0.15 to 0.34). VO2peak increased in AT versus UC by 4.1 (2.0 to 6.3) mL O2/min/kg and in AT versus RT by 2.7 (1.1 to 4.3), but not in RT versus UC 1.4 (-0.6 to 3.5). MVC increased in RT versus UC by 0.25 (0.01 to 0.48) Nm/kg, but not in RT versus AT 0.17 (-0.02 to 0.36) or AT versus UC 0.08 (-0.16 to 0.31)). CONCLUSION: AT and RT elicited improvements in physical capacity in PWMS. However, these improvements only moderately translated into improvements in physical function. Clinicaltrials.gov (NCT04913012) https://clinicaltrials.gov/study/NCT04913012.

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