OBJECTIVES This study evaluates the HTRS registry, developed as a collaboration to support the society research and a company post-marketing surveillance requirement for recombinant FVIIa in patients with congential hemophilia (CH) with alloantibody inhibitors (CHwI). METHODS The HTRS registry is a web-based second generation database. After IRB approval and informed consents, 83 sites participated in the registry from January 2004 to November 2008. RESULTS There are 2484 patients registered including 1696 with congenital hemophilia A or B. Median age was 13 years (range:0-85) for CH and 12 years (range:0-83) for CHwI. Non-Hispanic whites (CH:68%,CHwI:57%) and non-Hispanic blacks (CH:16%, CHwI:23%) were the largest racial/ethnic groups. The majority had little or no functional limitations (CH:77%, CHwI:66%). For CHwI patients, the median highest anti-VIII titers were 48BU (human) and 16BU (porcine). There were 6,517 acute bleeds captured (CHwI:6,025, rFVIIa:2,207). Acute bleed data was available for 429 CHwI patients, including 2,041 rFVIIa-treated bleeding episodes (first line:1851, second line:190). Approximately, 57% were spontaneous, 30% traumatic, 3% surgical, and 2% dental procedures. Bleeds were most frequent in joints (57%, 1163 bleeds), including ankle (448), knee (219) and elbow (292) bleeds. Others included muscle (20%), mucosal (7%), subcutaneous (6%), and head (3%). Median (range) total rFVIIa dose per treatment episode was 450 mcg/kg (46-43200 mcg/kg), with initial dose of 120 mcg/kg (37-400 mcg/kg), and 3 injections (1-480) over 1 day (1-99). Overall efficacy was 90%. Adverse events were rare. CONCLUSIONS For rare disorders, such as hemophilia complicated by alloantibody inhibitors, obtaining evidence-based outcomes through clinical trials is not always practical or statistically conclusive. The analysis of the significant amount of data accumulated over a 4-year period in the HTRS database represents an alternative approach to understanding the safety and efficacy of new therapeutic agents through the analysis of the “collective” experience of patients included in a longitudinal database.