The objective of this study was to evaluate the effect of spa therapy on clinical parameters of patients with gonarthrosis. Patients with gonarthrosis (n = 33) underwent a 2-week spa therapy using three treatment regimes and a 20-week follow-up as follows: group I (n = 11) had mineral water baths and hot native mineral mud packs, group II (n = 12) had mineral water baths and rinsed mineral-free mud packs and group III (n = 10) had tap water baths and mineral-free mud packs. The patients and the assessing rheumatologist were blinded to the difference in the treatment protocols. A significant improvement in the index of severity of the knee (ISK), as well as night pain scores, was achieved in group I. Improvement in physical findings and a reduction in pain ratings on a visual analogue scale (VAS) did not reach statistical significance. Analgesic consumption was significantly decreased in both groups I and III for up to 12 weeks. Global improvement assessed by patients and physician was observed in all three groups up to 16 weeks but persisted to the end of the follow-up period in group I only. Patients with gonarthrosis seemed to benefit from spa therapy under all three regimes. However, for two parameters (night pain and ISK) the combination of mineral water baths and mud packs (group I) appeared to be superior.