Abstract:[Objective] To investigate the clinical outcomes of total synovectomy and total knee arthroplasty (TKA) with or without radio- therapy in the treatment of knee advanced pigmented villonodular synovitis (PVNS). [Methods] A retrospective study was done on 39 pa- tients who received treatment for knee advanced PVNS from June 2007 to June 2019. According to the doctor-patient communication, 20 pa- tients received total synovectomy and TKA, followed by postoperative extra-articular radiotherapy (the RT group), while the remaining 19 pa- tients received total synovectomy and TKA only (non-RT group). The perioperative, follow-up and imaging data of the two groups were com- pared. [Results] There were no significant differences in operation time, total incision length, intraoperative blood loss, pain VAS score 5 days after surgery, walking time and hospital stay between the two groups (P>0.05). As time went during the follow- up period lasted for (36.0±2.2) months in a mean, the VAS scores significantly reduced (P<0.05), whereas the HSS, KSS functional scores, KSS clinical scores and knee range of motion (ROM) significantly increased in both groups (P<0.05). The last follow-up, the RT group proved significantly supe- rior to the non-RT group in terms of VAS [(1.7±0.5) vs (2.6±0.6), P<0.001], HSS [(93.6±2.2) vs (87.1±2.1), P<0.001], KSS functional score [(93.3±2.0) vs (87.3±1.9), P<0.001], KSS clinical score [(93.9±1.4) vs (87.7±1.8), P<0.001] and knee ROM [(144.4±6.1)° vs (136.9±3.8)°, P< 0.001]. By the latest follow-up, the RT group was significantly better than the non-RT group in recurrence rate (0% vs 21.1%, P<0.047). Re- garding imaging, the thickness of suprapatellar effusion and suprapatellar synovial were significantly reduced in both groups after operation (P<0.05). At the last follow-up, the RT group proved significantly superior to the non-RT group in terms of effusion thickness of suprapatel- lar bursae [(1.4±0.5) mm vs (2.6±0.7) mm, P<0.001] and synovial thickness of suprapatellar bursae [(0.9±0.2) mm vs (1.8±0.5) mm, P< 0.001]. However, there was no significant difference in the T value of bone mineral density between the two groups at any time points accord- ingly (P>0.05). [Conclusion] For knee advanced PVNS with severe bone destruction, total synovectomy and TKA with postoperative adju- vant radiotherapy does effectively prevent recurrence, with good safety, and achieve considerably better short-term clinical outcome over the counterpart without adjuvant radiotherapy.