This study aimed to evaluate the efficacy of manual therapy (MT) for patients with rotator cuff (RC) tendinopathy. RC tendinopathy is a common musculoskeletal disorder. MT is an intervention frequently used by physiotherapists for this condition although evidence regarding its efficacy is inconclusive. A literature search using terms related to shoulder, RC tendinopathy, and MT was conducted in 4 databases to identify randomized controlled trials (RCTs) that compared MT to any other type of intervention to treat RC tendinopathy. RCTs were assessed with the Cochrane Risk of Bias Tool. Meta-analyses or qualitative synthesis of evidence were performed. Twenty-one studies were included. The majority had a high risk of bias with only 5 studies having a score of 69% or greater, indicative of moderate to low risk of bias. A small but statistically significant overall effect for pain reduction of MT compared with a placebo or in addition to another intervention was observed (n=406) which may or may not be clinically important given a mean difference of 1.1(95% confidence interval [CI]: 0.6, 1.6) on a 10 cm visual analog scale (VAS). Adding manual therapy to an exercise program (n=226) significantly reduced pain and this effect may or may not be clinically important (mean difference of 1.0; 95%CI: 0.7, 1.4 on a 10 cm VAS). Based on qualitative analyses it is unclear that MT used alone or added to exercises improves function. Conclusions For patients with RC tendinopathy, based on low to moderate quality evidence, MT may reduce pain but it is unclear if it could improve function. More methodologically sound studies are needed before more definitive conclusions can be made.