Objectives. Open, prospective study to evaluate the effect of spa therapy on generalized osteoarthritis (GOA). Methods. Patients diagnosed as GOA were recruited from a private outpatient clinic. The treatment protocol was designed with 6 different spa modalities, 3 for each consecutive day, during 18 days. Interventions were Berthollet's technique (local mineral water cloud application), peloidotherapy, hydrotherapy, under water/standard (dry) massage, supervised water exercise, bath in hydro-massage pool, bath in tub with hydro-jets, free immersion in mineral water pool. The primary outcome was a clinically relevant improvement in 50% of patients at the end of the treatment. Statistical analyses were based on intention-to-treat method. Health care providers were blinded to the study. Results. Ninety nine patients were included between March 7th-April 29th 2011 and all were analyzed for the primary outcome. Clinically relevant improvement was observed in 61% of the patients at the end of the treatment, and 68% at the 8th month. Patient acceptable symptom state was achieved in 33% of the patients at the 3rd week and 75% at the 8th month and Outcome Measures in Rheumatology-Osteoarthritis Research Society International Criteria (OMERACT-OARSI criteria) response in 41% of the patients at the 3rd week and 19% at the 8th month. Improvement was also observed in other judgment criteria evaluating pain, function and quality of life and continued until the 8th month for some of the parameters. No serious adverse effect was observed. Conclusions. Spa treatment may improve the clinical status of patients with GOA and seems to be well tolerated.