This study examined the feasibility of using home telehealth monitoring to improve clinical care and promote symptom self-management among veterans with multiple sclerosis (MS). This was a longitudinal cohort study linking mailed survey data at baseline and 6-month follow-up with information from home telehealth monitors. The study was conducted in two large Department of Veterans Affairs (VA) MS clinics in Seattle, Washington, and Washington, DC, and involved 41 veterans with MS. The measures were demographic information and data from a standardized question set using a home telehealth monitor. Participants reported moderate levels of disability (median Expanded Disability Status Scale [EDSS] score, 6.5) and substantial distance from the nearest VA MS clinic (mean distance, 93.6 miles). Of the participants, 61.0% reported current use of MS disease-modifying treatments. A total of 85.4% of participants provided consistent data from home monitoring. Overall satisfaction with home telehealth monitoring was high, with 87.5% of participants rating their experience as good or better. The most frequently reported symptoms at month 1 were fatigue (95.1%), depression (78.0%), and pain (70.7%). All symptoms were reported less frequently by month 6, with the greatest reduction in depression (change of 23.2 percentage points), although these changes were not statistically significant. Home telehealth monitoring is a promising tool for the management of chronic disease, although substantial practical barriers to efficient implementation remain.