© 2017 Elsevier B.V. Background There has been remarkable growth in research examining physical activity behavior (any bodily movement produced by skeletal muscle contraction that results in energy expenditure) among people living with multiple sclerosis (MS) over the past decade. The current meta-analysis quantified physical activity participation levels in persons with MS compared with non-diseased and other clinical populations. Methods We searched PUBMED, PsycINFO and Web of Science using the keywords physical activity, exercise, and physical fitness in conjunction with MS. We conducted a quantitative synthesis of the difference in physical activity participation levels among persons with MS compared with non-diseased populations and other clinical populations and then examined moderators that might explain variation in the overall effect size (ES). Results 21 studies were included involving 5303 persons with MS and yielded a mean ES of −0.57 (95% CI=−0.76, 60.37). The weighted mean ES was heterogeneous (Q=443.811, df=31, p<0.001). The magnitude of the mean ES increased when comparing the MS population with non-diseased populations, but decreased when comparing MS with clinical populations. Conclusion The cumulative evidence reinforces that persons with MS are less physically active than non-diseased, but not clinical populations, and this observation supports the need for new efforts on promoting physical activity across the MS community.