BACKGROUND: Osteoarthritis (OA) is a public health problem that will probably increase in the future with the aging of the population. Crenobalneotherapy is commonly used to treat OA, but evidence from previous reviews was not sufficient. This systematic review aimed to identify the best evidence for the clinical effect of crenobalneotherapy for knee OA. METHODS: We systematically searched MEDLINE via PubMed, PEDRO and the Cochrane Central Register of Controlled Trials for articles published up to September 2015. Articles were included if trials were comparative, if one or more of the subgroups had knee OA with separate data, and if spa therapy or any hydrotherapy techniques involving mineral water or mineral mud was compared to any other intervention or no treatment. Statistical validity, external validity and quality of side effects assessment were evaluated by personal checklists. Risk of bias was assessed by the CLEAR NTP. RESULTS: Treatments (hot mineral water baths, mud therapy, hot showers, and sometimes massage and supervised water exercises) delivered in spa centers across Europe and the Middle East seem to improve symptoms in knee OA. They may be effective for pain and function. There are conflicting results about the effect on quality of life and drug consumption. CONCLUSIONS: Improvements with spa therapy for knee OA appear to be clinically relevant until 3 to 6 months and sometimes 9 months.