Movement variability during repetitive performance of a dynamic activity (eg, running, jumping, kicking) is considered an integral characteristic of optimal movement execution; however, its relationship with musculo-skeletal injury is not known. The primary aim of this study was to review published comparison trials to determine whether movement variability differs between uninjured controls and subjects with a lower limb musculo-skeletal injury. A systematic search of online databases; MEDLINE, Sports Discus, Scopus, and Web of Science was conducted from July to November 2016. Studies were selected if they (a) included participants with a lower limb injury, (b) compared injured participants to uninjured controls, (c) examined movement variability for at least one dependent variable, and (d) provided a statistical between-group comparison when comparing measures of movement variability. Studies were excluded if they (a) investigated neurological disorders, (b) examined musculo-skeletal injury in the upper extremity or spine, and (c) used nonlinear measures to examine variability (ie, complexity). A significant difference between injured and uninjured populations was reported in 73% of the included studies, and of these, 64% reported greater movement variability in the injured group. This is the first systematic review with a best-evidence synthesis investigating the association between movement variability and musculo-skeletal injury. Findings suggest that movement variability in those with a musculo-skeletal injury differs from uninjured individuals. Interestingly, there was an overall trend toward greater movement variability being associated with the injured groups, although it should be noted that this trend was not consistent across all subcategories (eg, injury type). For a clearer insight into the clinical application of variability, greater methodological homogeneity is required and prospective research is recommended.