Background: A large volume of systematic reviews and meta-analyses has been published on the effectiveness of sports injury prevention programs. Purpose: To provide a qualitative summary of published systematic reviews and meta-analyses that have examined the effectiveness of sports injury prevention programs on reducing musculoskeletal injuries. Study Design: Systematic review; Level of evidence, 4. Methods: We searched the PubMed, CINAHL, EMBASE, and the Cochrane databases for systematic reviews and meta-analyses that evaluated the effectiveness of sports injury prevention programs. We excluded published abstracts, narrative reviews, articles not published in English, commentaries, studies that described sports injury prevention strategies but did not assess their effectiveness, studies that did not assess musculoskeletal injuries, and studies that did not assess sports-related injuries. The most relevant results were extracted and summarized. Levels of evidence were determined per the Oxford Centre for Evidence-Based Medicine, and methodological quality was assessed using the AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews, revised version). Results: A total of 507 articles were retrieved, and 129 were included. Articles pertaining to all injuries were divided into 9 topics: sports and exercise in general (n = 20), soccer (n = 13), ice hockey (n = 1), dance (n = 1), volleyball (n = 1), basketball (n = 1), tackle collision sports (n = 1), climbing (n = 1), and youth athletes (n = 4). Articles on injuries by anatomic site were divided into 11 topics: general knee (n = 8), anterior cruciate ligament (n = 34), ankle (n = 14), hamstring (n = 11), lower extremity (n = 10), foot (n = 6), groin (n = 2), shoulder (n = 1), wrist (n = 2), and elbow (n = 1). Of the 129 studies, 45.7% were ranked as evidence level 1, and 55.0% were evidence level 2. Based on the AMSTAR-2, 58.9% of the reviews reported a priori review methods, 96.1% performed a comprehensive literature search, 47.3% thoroughly described excluded articles, 79.1% assessed risk of bias for individual studies, 48.8% reported a valid method for statistical combination of data (ie, meta-analysis), 45.0% examined the effect of risk of bias on pooled study results, and 19.4% examined the risk for publication bias. Conclusion: This comprehensive review provides sports medicine providers with a single source of the most up-to-date publications in the literature on sports injury prevention.