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The aim of this study was to prospectively evaluate the long-termefficacy and tolerability of hyaluronic acid (HA) for the treatment of knee pain due to Kashin–Beck disease (KBD). A total of 113 patients with KBD-based knee pain were treated with a 3-week course of HA. Clinical assessments were performed for each patient at 0 (baseline), 1, 2, 4,8, 12, 24, and 52 weeks. The primary efficacy measure was the visual analog scale (VAS) pain score. The secondary efficacy measures included the WOMAC A (pain), B(stiffness), and C (function) scores; the total WOMAC score; and the global assessments by patients and physicians. Tolerability was evaluated based on adverse events (AEs) and physician reporting.