Context • Shoulder pain is one of the most common pain complaints reported by patients. Consensus is lacking on its ideal treatment, and many different treatments are available and used. Prolotherapy is an injection-based therapy that has shown significant results in treating many common musculoskeletal pain conditions, including osteoarthritis, lateral epicondylosis, and low-back pain. Objective • The study intended to evaluate the use of dextrose prolotherapy in the treatment of shoulder pain. Design • The research team performed a case study. Setting • The study occurred at the Medical Center at Southwest College of Naturopathic Medicine (Tempe, AZ, USA). Participant • The participant was a middle-aged male with a long-term history of untreated shoulder pain. Intervention • Injections were placed in the patient's glenohumeral joint space, the acromioclavicular joint, the subacromial space, and the insertion of the supraspinatus. Each location was injected with a solution of 50% dextrose diluted with 1% lidocaine, 0.25% bupivacaine, and 1 mg methylcobalamin. The final concentration of dextrose in the solution was approximately 22.8%. Outcome Measures • The patient completed questionnaires (numerical rating scale, verbally reported at the beginning of each visit) indicating his level of pain on a scale of 0 to 10, with 0 = no pain and 10 = worst pain. Results • Following 3 sessions of prolotherapy, the patient reported a 90% reduction in pain and full restoration of normal activity. Conclusions • The findings suggest that dextrose prolotherapy may be an effective treatment for chronic shoulder pain and may be an alternative to surgery or other more costly and invasive interventions.