Purpose: To examine the possible contributions of capability, opportunity, and motivation for explaining long-term physical activity among people with multiple sclerosis and to report the results of a German survey study. Methods: The questionnaire, which was based on an expert interview study and behavior change theory, was structured and detailed applying the Theoretical Domains Framework. A total of 1027 people with multiple sclerosis provided data on sociodemographics, disease-related characteristics, and a set of constructs possibly related to long-term adherence. Participants were assigned to three groups: not regularly active, currently regularly active, and long-term regularly active. Eta squared was calculated to assess the magnitude of differences between groups using ANOVA. Results: Moderate or large differences between groups were identified for many domains within capability, opportunity, and motivation. For the following theoretical domains, large differences (eta(2) >= 0.140) were observed: Intention, Behavioural Regulation, Beliefs about Capabilities and Goals. Conclusions: Our results suggest that capability, opportunity, and motivation should be targeted simultaneously when designing future interventions. Inactive people with multiple sclerosis might benefit most from interventions increasing action self-efficacy and intention. Boosting autonomous motivation, goal setting, action planning as well as maintenance and recovery self-efficacy could have a positive effect on long-term adherence.