Background and Aim: Recurrent hemarthrosis results in synovitis and destructive arthropathy in hemophilic patients. The aim of our study was to investigate the efficacy and synovial changes with viscosupplementation therapy in treating hemophilic arthropathy of the knee. Subjects and Methods: Twenty hemophilic patients who had painful arthropathy of the knee with synovitis were enrolled. Patients received three weekly intra‑articular injections of 2 mL hyaluronic acid (HA). The synovial thickness and vascularity determined by ultrasonography, visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form 36 (SF‑36) were compared initially and at 1, 2, 3, and 6 months after the first injection. Statistical analysis was performed using SPSS version 20 software (Armonk, NY, USA: IBM Corp). Results: There were 19 hemophilia A patients and 1 hemophilia B patient. A total of 26 knees received viscosupplementation therapy. Significant improvement in VAS, SF‑36, WOMAC score, hyperemia, and thickness of suprapatellar recess synovium from baseline was seen up to 6 months after intra‑articular HA injection. No severe injection‑related adverse event was observed. Conclusions: This study suggests that three weekly intra‑articular HA injections are safe and effective in treating hemophilic arthropathy of knee with synovitis for a period up to 6 months. The treatment not only improved quality of life, pain and knee function but also reduced synovial thickness and hyperemia. HA viscosupplementation therapy could serve as an adjunctive therapy before arthroscopic synovectomy or total knee arthroplasty.