The therapeutic effects of mineral waters have been attributed to the inorganic components alone; however, biologically active organic components are also present. We aimed to investigate whether the healing effect of Szigetvár thermal mineral water could relate to the organic matter in patients suffering from osteoarthritis of the hips and the knees. XAD macroreticular resins were used to prepare the organic fraction. Patients received a 30-min thermal water (34°C) treatment in a bath tub, five times a week for 3 weeks. After randomization, patients were divided into three groups: tap water, mineral water, and organic fraction group. Primary outcomes were range of movement (ROM), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and visual analog scale (VAS) for pain severity, and the Short Form 36 (SF-36) questionnaire was used. These scores and indices were measured at baseline, after the last treatment, and at the end of the 3-month follow-up period. Seventy-four patients (age 67.3 ± 4.48 years) were enrolled: tap water n = 24, mineral water n = 26, and organic fraction n = 24. Treatment with the redissolved organic fraction significantly improved ROM, WOMAC, and SF-36 scores compared to the tap water. Our clinical trial provided evidence for the beneficial health effects of the organic fraction of Szigetvár medicinal water.