Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) has been used for many years in the successful management of bleeding episodes in patients with hemophilia and inhibitors. More recently, rFVIIa has also shown considerable success as a hemostatic agent in trauma and surgery patients without pre-existing coagulopathy. Despite extensive and varied usage of rFVIIa, the incidence of serious adverse events associated with its use is less than 1%; however, there remain concerns regarding the agent's potential to induce thrombosis. This paper will review the safety profile of rFVIIa by examining existing clinical evidence, and will demonstrate that the isolated thrombotic events reported following rFVIIa treatment are due primarily to an improvement in the coagulation mechanism rather than rFVIIa treatment per se. The demonstrated safety of rFVIIa is probably due to its localization to injured areas of the vascular tree by binding to tissue factor (TF) and activated platelets at the bleeding site, thus avoiding systemic activation of coagulation. Finally, those situations in which rFVIIa therapy may not be safe, such as disseminated intravascular coagulation (DIC) and sepsis, will also be discussed.