OBJECTIVE The objective of this study was to evaluate the effectiveness and long-term outcome of the treatment of patients with diffuse pigmented villonodular synovitis (PVNS) of the knee with subtotal arthroscopic and open synovectomy and subsequent external-beam radiotherapy. METHODS Eight patients diagnosed with diffuse PVNS by clinical and magnetic resonance imaging were treated surgically with subtotal arthroscopic synovectomy and an additional posterior incision for extra-articular lesions, followed by local adjuvant radiotherapy. These patients were followed up for a mean of 8.6 years to monitor remaining lesions and to detect new occurrences of the condition. RESULTS None of the patients presented with major postoperative complications or have had radiotherapeutic late effects. In no case was radiographic arthritis progression detected. Three patients exhibited late minor complications (peripatellar pain, articular effusion, and persistent quadricipital muscle atrophy). Only 1 patient (12.5%) presented with recurrence of the disease during the follow-up period. CONCLUSIONS On the basis of our limited study, subtotal arthroscopic and open synovectomy with subsequent local external-beam radiotherapy had a recurrence rate of 12.5% at 8.6 years of follow-up for the treatment of diffuse PVNS of the knee joint. METHODS Level IV, therapeutic case series.