Objective: The aim of this clinical trial was to evaluate the effect of 15 myofascial therapy treatments using ischemic compression on shoulder trigger points in patients with chronic shoulder pain. Methods: Forty-one patients received 15 experimental treatments, which consisted of ischemic compressions on trigger points located in the supraspinatus muscle, the infraspinatus muscle, the deltoid muscle, and the biceps tendon. Eighteen patients received the control treatment involving 15 ischemic compression treatments of trigger points located in cervical and upper thoracic areas. Of the 18 patients forming the control group, 16 went on to receive 15 experimental treatments after having received their initial control treatments. Outcome measures included a validated 13-question questionnaire measuring shoulder pain and functional impairment. A second questionnaire was used to assess patients' perceived amelioration, using a scale from 0% to 100%. Outcome measure evaluation was completed for both groups at baseline after 15 treatments, 30 days after the last treatment, and finally for the experimental group only, 6 months later. Results: A significant group x time interval interaction was observed after the first 15 treatments, indicating that the experimental group had a significant reduction in their Shoulder Pain and Disability Index (SPADI) score compared with the control group (62% vs 18% amelioration). Moreover, the patients perceived percentages of amelioration were higher in the experimental group after 15 treatments (75% vs 29%). Finally, the control group subjects significantly reduced their SPADI scores after crossover (55%). Conclusion: The results of this study suggest that myofascial therapy using ischemic compression on shoulder trigger points may reduce the symptoms of patients experiencing chronic shoulder pain.