Joint hemorrhage and subsequent hemophilic arthropathy are significant complications in hemophilia. The pathophysiology involves inflammation and angiogenesis. Cyclooxygenase-2 (COX-2) inhibitors are anti-inflammatory agents which have potent anti-inflammatory, anti-angiogenic and analgesic properties yet do not affect platelet function in the manner of traditional NSAIDs. These properties make such agents potentially useful as adjunctive therapy in hemophilia. There is only one prior report describing rofecoxib treatment in a single hemophilia patient. Our objectives were to determine the safety and efficacy of rofecoxib in treating acute hemarthrosis, chronic synovitis, target joints and pain We conducted a retrospective medical record review of patients treated with rofecoxib for acute hemarthrosis, chronic synovitis, target joint or pain. The safety and efficacy of rofecoxib treatment were determined based on subjective patient reports and physical examinations during follow-up clinic visits. Safety was determined based on adverse side effects. Efficacy in treating acute hemarthrosis was determined by comparing consecutive bleeds treated without and with rofecoxib and judged subjectively as effective, partially effective or ineffective. Efficacy for chronic synovitis and pain was judged subjectively with the 3 point scale described above. Efficacy in resolution of target joints was judged as effective if the target joint resolved or ineffective if it did not resolve. A total of 28 patients between 3-37 years of age were treated for a total of 42 courses of rofecoxib treatment. All courses were evaluated for safety and 31 for efficacy. Rofecoxib was used for 8 acute hemarthroses, 4 target joints, 7 cases of synovitis and 12 episodes of pain. Efficacy was demonstrated particularly for chronic synovitis and pain and no serious adverse events occurred. This is the largest study to date evaluating COX-2 inhibitors as adjunctive therapy in hemophilia. This study suggests that rofecoxib is safe and may be an important adjunctive therapy in the management of hemophilia.