Osteoarthritis of the knee joint is a public health concern with considerable social impacts and related-costs. Among the treatments available, several benefits of bathing in natural mineral water have been proposed: (1) to identify possible health benefits (in terms of effects on dimensions of pain, functionality, emotional and social aspects, and quality of life) of a 3-week balneotherapy intervention in patients with knee osteoarthritis; (2) to assess the clinical relevance of any benefits detected; and (3) to determine if these effects persist. Participants of this randomized controlled trial (RCT) were 120 patients randomly assigned to (1) an experimental group (3 weeks of balneotherapy consisting of daily whirlpool baths, hydrokinesitherapy sessions, and knee shower/massages) or (2) control group in which no form of treatment apart from their usual analgesia medication was given. Treatment benefits were assessed using the following tools: (1) visual analogue scale (VAS) of pain, (2) Timed Up & Go Test (TUG), (3) WOMAC osteoarthritis questionnaire, and (4) SF 36 health survey questionnaire. In the experimental group, these tests were conducted immediately before treatment, immediately after treatment, and at 3 months of follow-up. Patients assigned to the control group were assessed at the study start and 3 months later. Data processing and statistical analysis were performed using the SPSS (Statistical Package for Social Science) version 22.0. Out of 60 patients in the experimental group, 45 were found to benefit from the treatment intervention in terms of pain relief among other aspects, and also when test scores were compared to those obtained in the control group. Improvements were often clinical relevant and in most patients persisted 3 months after treatment onset.