The development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has provided an effective, alternative treatment strategy for hemophilia patients with inhibitors. However, its short half-life necessitates frequent infusions and results in high treatment costs. One potential solution to this problem may lie in the use of FVIIa gene transfer, which would achieve long-lasting therapeutic levels of expression from a single injection. Studies in animal models have shown that a recombinant adeno-associated viral vector can be used to insert both murine and human FVIIa into murine liver. Following FVIIa gene transfer, mice with hemophilia B demonstrated a long-term, dose-dependent increase in circulating levels of FVIIa, reduced prothrombin time, and correction of activated partial thromboplastin time into the normal range. In addition, blood loss following a modified tail-clip assay was significantly reduced. Ongoing studies in mice engineered to express a wide range of FVIIa levels aim to analyze organ histology and evaluate long-term survival, reproductive fitness, and real-time in vivo clot formation in the microvasculature. These studies are expanding our knowledge of the effects of continuously expressed rFVIIa, and it is hoped that they may eventually provide a new avenue for treatment of hemophilia.