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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. 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. Moderate or large differences between groups were identified for many domains within capability, opportunity, and motivation. For the following theoretical domains, large differences (η2 ≥0.140) were observed: Intention, Behavioural Regulation, Beliefs about Capabilities and Goals. 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. This study applied the COM-B model and Theoretical Domains Framework to identify a set of constructs for explaining long-term physical activity among people with MS. Behaviour change and maintenance interventions for people with MS should include techniques that foster intention, perceived self-efficacy and self-regulatory skills, and promote goal setting and autonomy of motivation for regular physical activity. Although barriers of the physical and social environmental context did not seem to be that important in our sample, scientists should consider addressing them in interventions for inactive and more disabled people with MS. Information about the benefits of physical activity should be regularly provided in MS rehabilitation, while further research should explore the relevance of information provision and knowledge for behaviour change in different groups of people with MS. [ABSTRACT FROM AUTHOR]