OBJECTIVES Frequent bleeding episodes within joints (hemarthrosis) in patients with congenital hemophilia with alloantibody inhibitors (CHwI) can result in the development of target joints with eventual functional disability. Clinical trials have assessed the efficacy of rFVIIa in the treatment of hemarthroses. Such studies have not been designed to address whether specific joints are more difficult to treat. The HTRS Registry is a collaborative effort between HTRS and Novo Nordisk to understand the efficacy and safety of rFVIIa and expand knowledge about treatment of hemophilia. METHODS We analyzed data from 2041 rFVIIa-treated bleeds in the HTRS registry (January 2004-November 2008) to identify hemarthroses in patients with CHwI. RESULTS There were 1163 hemarthroses treated with rFVIIa (first line:1,065, second line:98). Median age at time of bleed was 9yrs (range:0-60). The 798 non-target (NT) and 344 target (T) joint bleeds included (NT/T): ankle (279/169); elbow (202/90); knee (143/76); shoulder (46/5); foot (45/1); wrist (43/1); hand (43/0) and hip (24/4). Median (range) total rFVIIa dose per treatment episode for non-target joints was 400mcg/kg (46-18130mcg/kg) and for target joints was 630mcg/kg (50-21392mcg/kg). Total dosing varied by joint and was higher for target joints (NT/T): ankle (300/650); knee (360/558); elbow (490/556); hip (494/884); shoulder (720/1080). Overall efficacy for all joint bleeds was 90%, and for target joints was 90%. CONCLUSIONS For rare disorders, such as congenital hemophilia with inhibitors, obtaining evidence-based outcomes for data subsets through clinical trials is not always practical. The HTRS registry provides another large dataset and allows for comparison of clinically effective dosing regimens for treatment of non-target/target joints and across different joints. The data shown have implications for the design of future trials and in the analysis of trial results to account for variability in different joint bleeds between trial arms.