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To evaluate the evidence on the effectiveness of myofascial release therapy to relieve chronic musculoskeletal pain and to improve joint mobility, functioning level, and quality of life in pain sufferers.Randomized controlled trials were systematically gathered from CENTRAL, Medline, Embase, CINAHL, Scopus, and PEDro databases. The methodological quality of articles was assessed according to the Cochrane Collaboration’s domain-based framework. In addition, the effect sizes of main outcomes were calculated based on reported means and variances at baseline and in follow-up.Of 513 identified records, 8 were relevant. Two trials focused on lateral epicondylitis (N = 95), two on fibromyalgia (N = 145), three on low back pain (N = 152), and one on heel pain (N = 65). The risk of bias was considered low in three and high in five trials. The duration of therapy was 30–90 minutes 4 to 24 times during 2–20 weeks. The effect sizes did not reach the minimal clinically important difference for pain and disability in the studies of low back pain or fibromyalgia. In another three studies with the high risk of bias, the level of minimal clinically important difference was reached up to two-month follow-up.Current evidence on myofascial release therapy is not sufficient to warrant this treatment in chronic musculoskeletal pain.