The aims of this study were to evaluate whether balneotherapy with mineral sulphate-bicarbonate-calcium water could determine substantial symptomatic improvement, and to detect any changes in the quality of life (QoL) of patients with symptomatic knee osteoarthritis (OA). This was a prospective randomized, single blind controlled trial. Sixty outpatients with primary bilateral knee OA, according to ACR criteria, were included in the study and randomized to one of two groups: group I (30 patients) was treated with a daily sulphate-bicarbonate-calcium mineral water bath; group II (30 patients), the control group, continued their regular outpatient care routine. At baseline, after 15 days and after 12 weeks, patients were evaluated by Visual Analogue Scale (VAS) for spontaneous pain, Lequesne and Womac Index for gonarthrosis, SF-36, Arthritis Impact Measurement Scale (AIMS) and symptomatic drugs consumption. We observed a significant improvement of all parameters at the end of the cycle of balneotherapy which persisted throughout the follow-up period, whereas in the control group no significant differences were noted. This symptomatic effect was confirmed by the significant reduction of symptomatic drugs consumption. The differences between the two groups were significant for all considered parameters already from the 15th day and persisted during follow-up. Tolerability of balneotherapy seemed to be good, with light and transitory side effects. Our results confirm that the beneficial effects of balneotherapy in patients with knee OA last over time, with positive effects on the painful symptomatology, a significant improvement on functional capacities and QoL. Balneotherapy can represent a useful backup to pharmacological treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments.