Musculoskeletal injury (MSI) contributes to global health burdens. Effective MSI prevention is necessary. MSI risk factor screening tools can be used by employers to identify and mitigate occupational hazards. Rigorous synthesis of the effectiveness of these tools has not taken place. We synthesized literature on effectiveness of MSI risk factor screening tools for reducing injury through informing prevention interventions. A literature search of Medline, Embase, Cochrane Library (Trials), CINAHL, Scopus and PsycINFO databases was performed. Included studies required an analytic design, used an MSI risk factor screening tool to inform an intervention in a working-age population and reported an outcome of MSI development, injury or compensation/work absence. Data extraction and study quality rating (Downs and Black criteria) were completed. Studies were sub-categorized as having used a single MSI screening tool (single-tool) to inform an injury prevention intervention or involving multiple simultaneous screening tools (multiple-tool). Study outcomes were synthesized when possible. Eighteen articles representing fourteen studies met our inclusion criteria. No high-quality studies were identified (maximum Downs and Black score of 19). Studies did not employ previously validated tools but instead, typically, those purpose-built for a single use. The results were inconsistent both when using tools alone and in combination with other tools. Outcome measure heterogeneity precluded meaningful meta-analysis. There is limited evidence regarding use of MSI risk factor screening tools for preventing injury. Rigorous studies that utilize previously validated tools are needed.