Using meta-analytic procedures, this study involved a quantitative synthesis of the difference in physical activity among individuals with multiple sclerosis (MS) compared with nondiseased and diseased populations and then examined factors (i.e., moderators) that explain variation in the overall difference in physical activity. We searched MEDLINE, PsycINFO and Current Contents Plus using the key words physical activity, exercise and physical fitness in conjunction with multiple sclerosis; conducted a manual search of bibliographies of the retrieved papers; and contacted study authors about additional studies. Overall, 53 effects were retrieved from 13 studies with 2360 MS participants and yielded a weighted mean effect size (ES) of -0.60 (95% CI = -0.44, -0.77). The weighted mean ES was heterogenous, Q = 1164.11, df = 52, P < 0.0001. There were larger effects with objective versus self-report measures of physical activity, nondiseased versus diseased populations and primary progressive versus relapsing remitting MS. The cumulative evidence suggests that individuals with MS are less physically active than nondiseased, but not diseased, populations.