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Abstract Background Physical rehabilitation services are an important component of treatment for persons with multiple sclerosis (PwMS) to improve and maintain physical mobility. However, PwMS often have significant barriers to outpatient physical therapy (PT) services including mobility deficits and lack of transportation. The integration of exercise gaming (exergaming) and telehealth into clinical PT practices may overcome these barriers. The overarching purpose of this pilot study was to evaluate the acceptability and effects of an individualized telePT intervention using exergaming. Methods Ten individuals with multiple sclerosis (MS) completed a 12-week exergaming (Jintronix®) telerehabilitation intervention. In order to measure the acceptability of the telerehabilitation intervention, adherence was measured through the tablet-based rehabilitation software and each participant completed a satisfaction questionnaire. Clinical outcome measures were assessed at baseline and post-intervention. To evaluate the efficacy of this intervention, the following measures of physical function and fatigue were included; the Short Physical Performance Battery (SPPB), 25-Foot Walk (25FW), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale-12 (MSWS), and the 2-Minute Walk Test (2MWT). Clinical outcomes were analyzed using the Sign test and Wilcoxon signed rank test. All other data were evaluated using descriptive statistics. Results After the intervention, participants demonstrated significant improvements in ambulation speed during the 25FW (p = 0.04) and ambulation distance during the 2MWT (p = 0.002). Statistically significant increases of SPPB total score (p = .04) and sub-scores were also found. Participants did not demonstrate significant changes in the MFIS (p = 0.31) or MSWS-12 (p = 0.06) after the intervention. Participants had a 58.3% adherence rate during the intervention and performed their exercise program an average of 2.5 times per week. All participants reported that they were either ‘satisfied or ‘very satisfied’ with their telerehabilitation experience, would use telerehabilitation again, and would recommend telerehabilitation to others. Conclusion This individualized telerehabilitation intervention which integrates exergaming and clinical video teleconferencing is acceptable to patients and may offer a viable alternative to traditional PT for PwMS. Trial registration NCT03655431 , retrospectively registered on August 31st, 2018.