Hemostatic disturbances are common in patients undergoing hematopoietic stem cell transplantation (HSCT), and have a significant impact on morbidity and mortality. Graft-versus-host disease (GvHD), in which the donor's T lymphocytes mount an immune response against the recipient's cells, is a life-threatening condition that correlates strongly with the incidence and severity of bleeding episodes, highlighting the complex interaction between the hemostatic and immunological systems. Patients with GvHD of the gut also exhibit a deficiency of factor XIII (FXIII), further increasing the hemorrhagic risk. Among other risk factors for bleeding complications is use of the purified polyclonal immunoglobulin G (IgG), antithymocyte globulin (ATG). Although frequently used in preparative conditioning regimens, ATG may contribute to leukopenia, platelet reduction, and signs of disseminated intravascular coagulation (DIC). This paper will examine the cause and incidence of bleeding complications in patients undergoing HSCT, the potential contribution of GvHD and ATG to such bleeds, and the close interaction between the hemostatic and immune systems. The role of recombinant FVIIa as a hemostatic agent for the treatment of HSCT-associated hemorrhage will be briefly explored.