Patients with multiple sclerosis (PwMS) were shown to greatly benefit from multipronged exercise interventions comprising aerobic, resistance and corrective therapeutic components which result in endurance and strength improvement and reduction of fatigue and spasticity. However, telerehabilitation support of multipronged exercise programs in PwMS with significant mobility impairment has received limited attention. It is not clear whether severely disabled PwMS can successfully operate a telerehabilitation system at home independently. The goal of this study was to design a telerehabilitation system for individualized multipronged exercise programs and to assess the feasibility of the initial prototype in PwMS with significant mobility impairment. Usability assessment was based on the evaluation of patient ability to successfully carry out a standardized list of common tasks necessary to operate the system. For each task, time to completion, perceived difficulty and satisfaction were documented. Our results indicated a high level of acceptance of the system by these patients. On average, it took 83±41 seconds to complete all the major tasks necessary to operate the telerehabilitation system. After the initial introduction, all patients were able to successfully use the system and follow their individualized exercise prescription independently. A definitive systematic evaluation in a randomized clinical trial is warranted to demonstrate potential clinical impact of telerehabilitation in PwMS.