Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: People with Multiple Sclerosis (MS) face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation and travel distance. Generic mHealth exercise apps often fall short of what people with MS need to become physically active (i.e., exercise content that has been adapted to accommodate a wide range of functional limitations). Objective: This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with MS in a large randomized controlled trial (RCT) to engage in home-based telerehabilitation. Methods: Twenty-one participants with disabilities (10 people with MS) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design (UCD) approach, the development process included two stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through two usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated through a mixed methods approach. Results: Regarding app effectiveness, the second usability test resulted in an average of one problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to usefulness and satisfaction: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the RCT. Conclusions: A multi-level user-centered development process resulted in an inclusive exercise program for people with MS operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (i.e., people with varying levels of MS).