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Background: Platelet-rich plasma (PRP) injections have been introduced to augment the recovery of patients with shoulder pathology. Although multiple studies have been published, no large-scale trials or meta-analyses have assessed the efficacy of nonoperative shoulder PRP injection., Objective: To assess the efficacy of nonoperative PRP shoulder injection in rotator cuff pathology for pain as measured by the visual analog scale (VAS) and range of motion (ROM)., Design: Two authors independently screened the Medline and Cochrane databases to include prospective studies that reported VAS and ROM outcomes for nonoperative shoulder PRP injections for rotator cuff pathology. Study quality was assessed using the revised Cochrane Collaboration risk-of-bias tool and modified Downs and Black checklist. Subsequent meta-analysis was performed to determine the effect of nonoperative PRP injections on pain and ROM 3 to 12 months after intervention., Results: Six studies met systematic review criteria. The included studies used different PRP formulations (concentration, leukocyte count), injection protocols (approach, injection number), and varied study designs. Three studies concluded that PRP provided no significant benefit for pain and ROM when compared to physical therapy. Within-group meta-analysis of six fairly heterogeneous studies (I 2 77.8%) demonstrated a statistically significant (P < .001) improvement in pain 3 to 12 months after PRP injection. Within-group meta-analysis for four studies for shoulder flexion and abduction was found to be too heterogeneous to derive meaningful results., Conclusion: There is a limited quantity of high-quality studies that assess the efficacy of nonoperative PRP shoulder injection for pain and ROM. Systematic review of PRP injections did not demonstrate an improvement in pain or ROM compared to physical therapy. Although within-group meta-analysis of nonoperative PRP statistically showed that nonoperative PRP improved pain, the lack of adequate negative controls precludes the ability to conclude whether improvements were due to natural recovery or nonoperative PRP., (© 2020 American Academy of Physical Medicine and Rehabilitation.)