© 2017 Human Kinetics, Inc. Background: Physical inactivity is common in persons with multiple sclerosis (MS), but there is very little known about the pattern and predictors of changes in physical activity over time. Purpose: This study examined changes in moderate-to-vigorous physical activity (MVPA) over a 30-month time period and the demographic and clinical predictors of such changes in relapsingremitting MS (RRMS). Methods: 269 persons with MS wore an accelerometer for a 7-day period and completed a demographic/ clinical scale every 6 months over a 30-month period. Data were analyzed using latent class growth modeling (LCGM). Results: LCGM identified a two-class model for changes in levels of MVPA over time. Class 1 involved higher initial levels of MVPA and linear decreases in MVPA over time, whereas Class 2 involved lower initial levels of MVPA and linear increases in MVPA over time. LCGM further indicated that males were more likely (OR = 5.8, P < .05) and those with higher disability status were less likely (OR = 0.51, P < .05) to belong to Class 1 than Class 2. Conclusion: Levels of MVPA change over time in persons with RRMS and the pattern of change suggests that behavioral physical activity interventions for persons with MS might target men and those with lower disability.