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Aim: To prospectively evaluate the long‐term efficacy and safety of repeated sodium hyaluronate injections for the treatment of knee pain due to Kashin‐Beck disease (KBD). Methods: A total of 85 patients with KBD‐based knee pain were treated with two cycles of a 5‐week course of sodium hyaluronate and received clinical assessments with a follow‐up period of 24 months after the first cycle. The primary efficacy measure was the visual analogue scale (VAS) pain score. The second efficacy measure included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores; and the patients' and physicians' global assessments. Tolerability was evaluated based on adverse events (AEs). Results: Seventy‐one patients (83.5%) completed the final study. The VAS was significantly reduced from 65.06 ± 12.21 mm (mean ± standard deviation [SD]) at baseline to 30.17 ± 11.92 mm at 6 months and was maintained for 24 months (35.79 ± 7.92 mm, P < 0.01 vs baseline). This finding was supported by the secondary variables (the WOMAC A, B and C scores; the total WOMAC scores; and the global assessments of the patients and their physicians at months 6, 12, 18 and 24). The overall incidence of AEs during the first and second cycles was 8 (9.4%) and 7 patients (8.2%), respectively. No serious AEs were reported. Conclusions: Repeated once yearly cycles of intra‐articular sodium hyaluronate injections may improve knee KBD symptoms during the inbetween cycle period as well as exert a significant carry‐over effect for at least 1 year after the repeated cycle. Other randomized double‐blind studies are needed to confirm the findings from our study. [ABSTRACT FROM AUTHOR]