Background: Rotator cuff lesions are one of the major causes of shoulder pain and dysfunction. Numerous non-surgical treatment modalities have been described for chronic rotator cuff lesions, but the debate continues over the optimal procedure. The aim of this report is to present the results of prolotherapy in the treatment of chronic refractory rotator cuff lesions. Hypothesis: Dextrose prolotherapy will reduce pain and improve shoulder function and patient satisfaction. Material and methods: We recruited 120 patients with chronic rotator cuff lesions and symptoms that persisted for longer than 6 months. Patients were divided into two groups: one treated with exercise (control group; n= 60) and the other treated with prolotherapy injection (prolotherapy group; n=60). In the latter, ultrasound-guided prolotherapy injections were applied under aseptic conditions. In the former, patients received a physiotherapy protocol three sessions weekly for 12 weeks. Both groups were instructed to carry out a home exercise program. Clinical assessment of shoulder function was performed using a visual analog scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), Western Ontario Rotatory Cuff (WORC) Index, patient satisfaction, and shoulder range of motion. Patients were examined at baseline, weeks 3, 6, and 12, and last follow-up (minimum of one year). Results: A total of 101 patients (44 controls and 57 in the prolotherapy group) completed all study protocols and were included in the study. Using a within-group comparison, both groups achieved significant improvements over baseline, as measured by the VAS, SPADI, WORC index, and shoulder range of motion (13 < 0.001). Using a between-group comparison, a significant difference was found in the VAS scores at baseline, weeks 3, 6, and 12, and last follow-up. In addition, significant differences were found in the SPADIs and WORC indices at weeks 6 and 12 and the last follow-up. Significant differences were found in shoulder abduction and flexion at week 12 and last follow-up, and in internal rotation at last followup. However, no significant was found in external rotation at any follow-up period. In the prolotherapy group, 53 patients (92.9%) reported excellent or good outcomes; in the control group, 25 patients (56.8%) reported excellent or good outcomes. Conclusion: Prolotherapy is an easily applicable and satisfying auxiliary method in the treatment of chronic rotatory cuff lesions. Study type: Randomized prospective comparative trial. (C) 2017 Elsevier Masson SAS. All rights reserved.