Background: Hemophilia is a bleeding disorder characterized by recurrent bleeding, especially in joints (hemarthrosis), leading to destructive effect to the most of joint components, resulting in synovitis, osteochondral degeneration, and eventually, end-stage hemophilic arthropathy. Objective: Since few published data exist about the influence of OPG (Osteoprotegrin) and RANKL (receptor activator of nuclear factor-kappa B ligand) in haemophilic arthropathy, the present study is conducted to investigate their serum level in hemophilic patients. Methodology: This study has been carried out on Iraqi patients with hemophilia in the National Center of Hematology/Mustansiriyah University. Forty male patients involved in this study with a range of (11-44) years old, Hemophilia A affected 25 of them, while the other 15 were hemophilia B. Along with patient group, 20 healthy subjects with matched age and gender were involved as control group. The presence and severity of arthropathy among patients was determined based activated partial thromboplastin time (aPTT)) in hemophilic patients, while RANKL and OPG were determined in the serum samples of healthy and patient subjects. Result: The serum level of RANKL in Hemophilia A patients was (204.6pg/ml) is significantly (p0.001) higher than in control (164.5pg/ml) and in Hemophilia B patients was (200pg/ml). While the serum level of OPG in Hemophilia A patients was (67.2pg/ml) is significantly (p0.002) higher than in control (30.21pg /ml) and in Hemophilia B patients (48.85pg/ml). Conclusion: It can be concluded that this system RANKL, RANK, and OPG are important for the metabolism of bones.