© 2019 Elsevier B.V. Background: The 6-minute walk (6 MW) is the most commonly applied measure of endurance walking capacity in persons with multiple sclerosis (MS); however, we are not aware of a quantitative synthesis of 6 MW performance in MS. Research question: We undertook a meta-analysis quantifying the overall magnitude of difference in 6 MW performance between MS and healthy controls (HCs), and then within MS as a function of disability status. We further examined possible moderator variables of 6 MW performance. Methods: The systematic search was conducted for articles that included the 6 MW in persons with MS and involved comparison groups (i.e., HCs or MS disability subgroups (i.e., mild vs moderate-to-severe disability status)). The mean and standard deviation of the distance traveled during the 6 MW as well as sample sizes were entered into Comprehensive Meta-Analysis software and we estimated the overall effect size (Cohen's d) using a random effects model and examined categorical variables as possible moderators (e.g., instruction protocol, provision of encouragement, method of distance measurement, and course description). Results: Thirty-four studies met inclusion criteria with a total sample size of 3204 persons (MS: 2683; HC: 521) yielding 42 total comparisons. Persons with MS walked a shorter distance than HCs (mean difference = –177.2 ± 19.1 m) with a large effect size (d = – 1.87). Persons with mild disability walked further than those with moderate-to-severe disability (mean difference = 185.19 ± 9.2 m) with a large effect (d = 1.83). The categorical variables of provision of encouragement and course layout moderated the effect of MS and course layout moderated the effect of disability status on 6 MW performance. Significance: This meta-analysis of 6 MW performance defines mean difference in 6 MW performance in MS compared with HCs and provides an estimate of the disease-related effect of MS on endurance walking capacity for application within clinical research and practice.