Background Yttrium-90 (90Y) is approved in several countries as a radiosynoviorthesis agent in the intra-articular treatment of synovitis, however, no such radiopharmaceuticals are approved in Canada. The aim of this Health Canada–approved study was to examine the safety and efficacy of 90Y synovectomy among patients with refractory synovitis. Methods We performed a subset analysis of a prospective, phase III, single-arm, pan-Canadian trial. Large and medium-sized joints of adults with refractory inflammatory mono- or oligo-arthritis and minimal cartilage/bone destruction who failed treatment with two intra-articular corticosteroid injections were eligible. Patient follow-up was at 3, 6 and 12 months. Outcome measures included joint tenderness, swelling, effusion, joint function and bone scans. Results A total of 79 joints were included (90% knees). The underlying diagnosis included SpA (35.2% of patients), RA (26.8%), JIA (8.5%) and other (29.6%). Non-biologic DMARDs were concurrently used in 59.2% of patients and biologic/targeted synthetic DMARDs in 31%. Five adverse events occurred, including one serious radiation burn requiring surgery. All events were non-life-threatening and resolved. Significant improvements in joint tenderness, swelling and effusion were achieved at 3 months (P Conclusion Our results confirm the safety of 90Y radiosynoviorthesis in refractory synovitis and provide preliminary evidence supporting its clinical efficacy with sustained benefit at 12 months, suggesting that it is a safe alternative to surgical synovectomy in such cases. This is the first such study in a Canadian cohort.