Background: The uptake of the Canadian Physical Activity Guidelines (PAGs) for adults with multiple sclerosis (MS) may be facilitated through delivery via telehealth. Telehealth involves the delivery of health services through telecommunications technologies such as mobile applications (apps) and offers many advantages including ease of access and tracking and monitoring PA thereby facilitating immediate feedback. To date, there is limited information regarding preferred features of an app for people with MS, and the few commercially-available apps specific to MS were developed by entrepreneurs without involvement from healthcare providers or researchers and an in-depth understanding of the needs and preferences of people with MS. Objectives: We utilized a qualitative research design to seek information on the needs and preferences of people with MS for a mobile application based on the PAGs. Methods: We adopted a pluralistic analytical approach by examining a rich pool of existing data through two different lenses to explore (i) what people with MS wanted in an app based on the PAGs and (ii) perceptions of an app based on the PAGs. Semi-structured interviews with 40 persons with MS from across the United States were conducted. Interview questions focused on desires and perceptions of potential approaches for increasing the uptake of the PAGs by people with MS. The data were subjected to deductive, content analysis to identify populous mentions of desired mobile applications based on the PAGs. We then used inductive, semantic thematic analysis to further identify, analyze and interpret the opinions and evaluations of participants. Results: The 3 themes identified were (1) strong evidence base, (2) app design, and (3) data-based guidance. The 1st theme centered around the inclusion of evidence-based content that offers exercises and information specific for MS. The 2nd theme included app features of activity tracking, reminders/prompts, and feedback. The 3rd theme involved guidance that was based on personal data for adapting the PAGs based on mobility level and abilities. Conclusions: The study provides evidence for the development of a mobile application for increasing the awareness and uptake of the PAGs by people with MS.