© 2016 American Congress of Rehabilitation Medicine Objective To synthesize the evidence for differences in cognitive motor interference (CMI) between persons with multiple sclerosis (MS) and those without MS by using systematic review and meta-analysis. Data Sources EMBASE, PubMed, ScienceDirect, Scopus, SPORTDiscus, and Web of Science. Our focused literature search was informed by past systematic reviews of CMI during walking in MS. Study Selection The key terms searched included Multiple sclerosis and synonyms of motor function (eg, Gait disorders, Gait, Walking, Balance, or Fall) and motor and cognitive functions (eg, Cognitive motor interference or Thinking). Data Extraction From the 116 abstract-identified articles, 13 experimental studies were selected for the final analysis and were rated using the Quality Assessment of Diagnostic Accuracy Studies tool. A meta-analysis was performed for all considered outcomes. Data Synthesis The results yielded a small overall effect size (ES) of.08 (SE=.17; 95% confidence interval, −.25 to.40; z=.49; P>.05), which indicated a nonsignificant minimal difference in CMI between persons with MS and those without MS. The moderator analysis for motor task (mobility task: ES,.22; postural task: ES, −.11) was not significantly different between persons with MS and those without MS. The moderator analysis for cognitive task (verbal fluency task: ES,.66; mental tracking task: ES,.04; discrimination and decision-making task: ES, −.30) resulted in a significant difference in CMI between persons with MS and those without MS (P<.05). Conclusions We provide evidence that overall there is a minimal difference in CMI between persons with MS and those without MS.