IntroductionMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with a prevalence of nearly 1 million adults in the United States. MS results in declines in physical activity and peak oxygen consumption that might be independently associated with declines in walking performance. Therefore our purpose was to evaluate the association between physical activity and peak oxygen consumption with walking performance in individuals with MS. MethodsFifty individuals with MS between the ages of 18–70 yrs. (Female: 38; 46 ± 12 yrs.; BMI: 28.5 ± 6.4; EDSS: 3.3 [IQR: 2.5–4]) performed a maximal incremental cycle test to assess peak oxygen consumption (VO2peak), and wore an accelerometer for one week to measure moderate-to-vigorous physical activity (MVPA). Subjects further completed a timed 25-foot walk test (T25FW) and 6-minute walk (6MW) to measure walking performance. ResultsMVPA and VO2peak were correlated with 6MW and T25FW (p < 0.05). When combined in multivariate regression analyses, VO2peak and MVPA were both significant contributors of T25FW speed and 6MW, but after controlling for sex and age, MVPA was the only significant contributor (β = 0.32 and β = 0.44, respectively). ConclusionBoth higher MVPA and VO2peak were associated with better walking performance and in a combined model physical activity, but not peak oxygen consumption, remained an independent contributor to walking performance in individuals with MS. These results suggest that improving MVPA is a potential target for interventions to improve walking performance in persons with MS.