Sixty-six patients suffering from chronic rotator cuff tendinopathy were randomized to receive neurofascial dextrose prolotherapy (n=33) or a control (n=33; a combination of transcutaneous electrical stimulation, pulsed ultrasound, superficial heat, and an exercise program) for pain relief. The primary outcome of interest included shoulder pain measured using the Shoulder Pain and Disability Index (SPADI). The secondary outcome of interest was shoulder disability measured using SPADI. Primary and secondary outcomes were measured at 2 weeks, and 3 months follow-up. Other outcomes of interest included total SPADI scores, incidence of adverse events, and number of patients reporting a pain reduction of 2.8 or more on the visual analogue scale (VAS). Results demonstrated that SPADI pain scores were significantly reduced in the dextrose prolotherapy group vs control at 2 weeks compared to baseline values (p<0.001). However, the change in SPADI pain scores at 3 months from 2 weeks were not significantly different between groups (p=0.055). The change in SPADI disability scores at 2 weeks from baseline were significantly favored in the dextrose prolotherapy group vs control, but this trend reversed at 3 months from 2 weeks (p<0.001 for all). No patients in either group experienced an adverse event.