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Objective: Despite the established success of total knee arthroplasty (TKA) with end-stage osteoarthritis, there is a notable scarcity of research on its long-term outcomes in individuals suffering from end-stage Kashin-Beck disease (KBD). This retrospective study aimed to assess the long-term outcomes and effectiveness of clinical function, quality of life, and complications of TKA and end-stage KBD patients in Tibetan highland areas., Methods: The retrospective cohort included 43 KBD patients, comprising a total of 59 knees, who had undergone TKA at West China Hospital, Sichuan University between 2008 and 2021. Patients were subsequently followed up for a minimum of 3 years, and received rigorous radiological and clinical assessments at 3, 6, and 12 months post surgery, followed by annual examinations thereafter. The evaluation included various efficacy indices, including visual analogue scale (VAS) scores, hospital for special surgery (HSS) scores, functional score for adult Tibetans with Kashin-Beck disease (FSAT-KBD), and radiographic findings. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test., Results: Throughout the average follow-up duration of 10.8 years, patients experienced a substantial reduction in knee pain and noteworthy functional improvement. The VAS scores decreased significantly from 77.47 ± 4.12 mm before surgery to 10.91 ± 1.97 mm after surgery, indicating considerable alleviation of knee pain. The HSS scores improved markedly, increasing from 44.26 ± 4.95 preoperatively to 91.26 ± 4.37, indicating enhanced joint function. Similarly, the FSAT-KBD exhibited positive progression, increasing from 25.90 ± 3.12 to 36.95 ± 3.54. Importantly, at the last follow-up, none of the patients presented with periprosthetic infection, prosthesis loosening, or periprosthetic fracture., Conclusion: At long-term follow-up, compared with patients in the preoperative period, patients in Tibetan highland areas with KBD of the knee who underwent TKA benefited from a significant reduction in pain, improvement in joint function, and satisfactory improvement in quality of life., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)