Background: Persistent knee synovitis leads to joint discomfort, incapacitating inflammation, and functional limitations. The conventional approach has involved surgical procedures to eliminate the actively inflamed synovial membrane. This study aims to investigate the recurrence-free survival and functional outcome after synovectomy and subsequent radiosynoviorthesis (RSO) in patients with knee synovitis. Methods: Thirty-seven knees diagnosed with pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), and peripheral spondyloarthritis underwent synovectomy and subsequent RSO between May 2005 and October 2016. The mean age was 34.9 ± 15.1 years, and the mean follow-up period was 84 ± 36.4 months. Clinical outcomes were assessed using the Oxford Knee Score and the presence of swelling and pain at the last follow-up. Recurrence-free survival denotes the duration from synovectomy to surgical re-synovectomy. Results: In general, twelve knees underwent re-synovectomy after a mean follow-up of 34.8 ± 24.9 months. The recurrence-free survival was 83.8% at two years, 71.3% at five years, and 61.7% at ten years. The subgroup analysis revealed recurrence-free survival at two years in 63.6% of patients with PVNS, 86.7% of those with RA, and 100% of individuals with peripheral spondyloarthritis. Conclusions: This study demonstrates that combined therapy for synovitis is an effective approach, significantly improving clinical outcomes.