To compare the effects of medical mud-pack (MMP) treatments applied at different temperatures on the pain and joint functions of patients with knee osteoarthritis (KOA). Kellgren Lawrence (KL) stage 3 or 4 KOA patients were included and randomized into three groups. Patients in groups 1, 2, and 3 took MMP treatment to both knees at 39 °C, 42 °C, and 45 °C, respectively. The treatment was performed for 12 days (only weekdays) and was 30 min long per day. The same blinded physician evaluated the patients at baseline and at the end of the treatment. The assessments were done before and after the intervention. The primary outcome was to achieve a minimal clinically important improvement (MCII) for KOA (decrease of at least 19 mm (-40.8%) on the VAS for pain, a decrease of 18.3 mm (-39%) on the patient's global assessment (PGA), and/or a decrease of at least 9.1 points (-26%) on the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (WOMAC-FS). Secondary outcomes were pain (VAS), patient's global assessment (VAS), physician's global assessment (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Patient's health state, Patient Acceptable Symptom State (PASS). 217 patients were analyzed. Groups 1, 2, and 3 had 68, 81,68 patients, respectively. The MCII measurement revealed that MMP treatment did not show a significant difference between groups 2 and 3 (p >
0.05). Also, it was observed that more patients in groups 2 and 3 reached the MCII compared to group 1 (p <
0.001). For the secondary outcomes, significant improvements were observed within-group evaluations for each of the three groups (p <
0.001). Between groups comparisons, the improvements at the end of the treatment were found to be superior for group 2 and group 3 compared to group 1 (p <
0.001). There was no statistically significant difference between groups 2 and 3 for any parameters (p >
0.05). The number of patients who achieved the PASS was statistically lower for group 1 compared to groups 2 and 3 (p <
0.001). We observed significant improvements in all groups after treatment. The main result, as measured by MCII, suggests that MMP treatments at 42-45 °C is more effective than at 39 °C in managing severe KOA patients' pain and functional status. We found no significant difference in pain and joint function improvement between 42 °C and 45 °C after MMP.