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Objective: Intra-articular injections of hyaluronic acid (HA) have been reported to alleviate pain, reduce disability, and improve joint function in glenohumeral osteoarthritis (GH-OA). This retrospective study aimed to evaluate the effectiveness of a HA-based formulation (Hyalubrix®) in reducing the pain of patients with GH-OA and improving both patient's shoulder functions and quality of life (QoL)., Methods: Data collected during the standard clinical practice of the center was retrospectively analyzed. The Simple Shoulder Test (SST) questionnaire reported data on the patient's ability to perform daily activities; the Euro-Quality of Life Health Assessment (EQ-5D) collected evidence on QoL; and changes in pain were evaluated through the Visual Analog Scale (VAS). SST and EQ-5D scores were analyzed comparing baseline values with those at the last follow-up, while VAS was investigated for all the available visits. Continuous values were summarized as mean ± standard deviation, median, and 25-75th percentiles. Shapiro-Wilk test assessed normality, with significance set at p<0.05, and no adjustments for multiple comparisons were made., Results: All scores showed a significant improvement: VAS decreased from 55.4±13.8 to 16.2±16.3 (p<0.001), the SST increased from 38.0 to 65.5 (p<0.001), as well as the EQ-5D (from 41.7 to 76.7; p<0.001)., Conclusions: GH-OA treatment with Hyalubrix® proved to be highly beneficial, leading to complete pain reduction in more than 50% of patients and a significant reduction in 27.5% of cases. This resulted in improved joint function and QoL.