<h3>Research Objectives</h3> To investigate the short-term effects of a spa rehabilitative protocol on pain perception, mood, and Quality of Life among patients affected by degenerative musculoskeletal disorders or post orthopaedic surgery outcomes. <h3>Design</h3> A multicenter observational study was conducted through pre- and post-treatment evaluations, planned follow-ups at three and six months were not conducted because of the COVID-19 pandemic. <h3>Setting</h3> The study was carried out in six spa facilities (Sirmione, Lombardy region, Italy; Abano Terme, Veneto region, Italy; Battaglia Terme, Veneto region, Italy; Levico Terme, Trentino Alto Adige region, Italy; Bibione, Veneto region, Italy; Casciana Terme, Tuscany region, Italy). <h3>Participants</h3> From March 2019 up to October 2019, data from the 160 users of the spa facilities with a medical prescription were collected. <h3>Interventions</h3> Twelve sessions of water-based exercise (thermal or warm water), six sessions per week, for a period of two weeks. A group of 44 patients also received traditional thermal therapies, including 12 mud therapy sessions and 12 thermal baths, six times each week, for two weeks. <h3>Main Outcome Measures</h3> Numerical Rating Scale (NRS), the Short Form Health Survey (SF-12), and the EuroQol-5D (EQ-5D). <h3>Results</h3> Data analysis has highlighted significant improvements in NRSp (p< 0.001), NRSa (p< 0.001), SF-12 PCS (p< 0.001), SF-12 MCS (p< 0.001), EQ-5D (p< 0.001), and NRSm (p=0.005) after the treatments. Different water types seemed to influence results, showing significant differences in NRSp, NRSa, NRSm, SF-12 PCS, SF-12 MCS and EQ-5D scores (p-value respectively, 0.003, < 0.001, < 0.001, < 0.001, < 0.001). <h3>Conclusions</h3> he spa environment in real-life demonstrated it could provide an out-of-hospital alternative for post-surgical patients. The addition of traditional thermal treatments should be a viable strategy for rehabilitation in degenerative conditions. <h3>Author(s) Disclosures</h3> No conflict of interests to declare.