73 patients with rotator cuff tendinopathy were randomized to one of three study treatment groups: (1) hypertonic dextrose prolotherapy injection directly to affected entheses, (2) saline injection directly to affected entheses, or (3) saline injection superficial to affected entheses. The purpose of this study was to investigate the clinical benefits of dextrose prolotherapy when compared to control groups by observing improved patient-reported pain scores, patient satisfaction scores, and ultrasound grading of regenerative effect. Results demonstrated that dextrose entheses injection resulted in significantly improved outcome scores when compared to superficial saline injection, but showed comparable scores with saline entheses injection.