Background: Chronic shoulder pain is a frequent musculoskeletal complaint that significantly affects function, productivity, and quality of life. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential regenerative option due to their anti-inflammatory and tissue-repair properties. This study aims to evaluate the safety and short-term effectiveness of intra-articular injections of umbilical cord-derived MSCs (UC-MSCs) in patients with chronic shoulder pain. Methods: A retrospective pragmatic observational study was conducted at the Regenerative Medicine Institute in Costa Rica. Medical records were reviewed to extract clinical, sociodemographic, and treatment-related variables. The primary outcome was functional improvement measured with the American Shoulder and Elbow Surgeons (ASES) score. Changes between baseline and the 3-month follow-up were analyzed using paired tests, effect size calculations, and regression models to explore predictors of treatment response. Results: Twenty patients met the inclusion criteria. A significant improvement in shoulder function was observed, with a mean ASES increase of 17.17 points, exceeding the minimum clinically important difference of 12. Sixty percent of patients achieved clinically meaningful improvement. Effect size estimates indicated a large magnitude of change. Regression analyses showed that baseline ASES predicted follow-up scores, while higher UC-MSC doses were associated with greater functional improvement. No adverse events were documented during the study period. Conclusions: The study shows that UC-MSC therapy is a safe, minimally invasive, and clinically beneficial option for chronic shoulder pain. These findings support the therapeutic potential of MSCs and highlight the need for larger controlled studies to validate long-term efficacy and optimize treatment protocols.