BACKGROUND: Arthroscopic repair is currently the gold standard for the surgical treatment of rotator cuff tears, but the retear rates remain unacceptably high. Mesenchymal stem cells (MSCs) may play a role in the local biology and enhance tendon-to-bone healing during rotator cuff repair. However, the scientific literature is still not well systematized on the effects of injection of MSCs as an augmentation tool for rotator cuff repair. Our goal was to investigate the effect of injections of MSCs to augment rotator cuff repair in patients with rotator cuff tear. METHODS: PubMed and EMBASE were searched up to June 2022 for clinical studies that applied MSCs injections to augment rotator cuff repair. Imaging, patient-reported outcomes measures, shoulder range of motion and strength were collected. Quantitative synthesis included within- and between-group mean differences with the within-group percentage of minimal clinically important difference for each study and continuous outcomes, and relative risks (RR) for retears and adverse events. Quantitative synthesis was computed with 95% confidence intervals (CIs). RESULTS: We included 5 studies comprising a total of 228 individuals with a weighted mean age of 59.3 ± 1.2 years. Three studies used bone marrow MSCs and two studies applied adipose-derived MSCs. Patient-reported outcomes measures, shoulder range of motion, and strength improved significantly in all MSCs groups, with minimal clinically important differences ranging from 120% to 679% of established cut-off. When compared to rotator cuff repair alone, the MSCs groups did not result in improved outcomes. The MSCs group showed significant protective effect at the mid-term (RR = 0.52, 95% CI 0.27-0.98) and long-term (RR = 0.24, 95% CI 0.11-0.53). CONCLUSION: There are no differences in clinical and functional outcomes between rotator cuff repair with or without augmentation with MSCs. However, there may be a protective effect against retear at the mid-term and long-term follow-up when augmenting the repair with MSCs. The literature on this topic is still preliminary and the quality and certainty of evidence is limited.