We have analysed the published literature on eptacog alfa (recombinant factor VIIa; rFVIIa) for nonhaemophiliac conditions with the aim of determining its current place in therapy. Initial surgical and/or medical management is required for any patient with life-threatening bleeding. In those with continued life-threatening bleeding (i.e. despite maximal surgical and/or medical therapy), eptacog alfa may be considered as additional therapy, in exceptional circumstances. There is good evidence from systematic reviews and randomized controlled trials (RCTs) that eptacog alfa stops bleeding in adults with intracerebral haemorrhage (ICH) if it is given within 4 hours of symptom onset. However, a recent phase III RCT suggests that it does not improve clinically relevant long-term outcomes (death and disability). There is also good evidence against prophylactic use of eptacog alfa during orthotopic liver transplantation or liver resection, and in treating variceal and nonvariceal haemorrhage in patients with cirrhosis. The evidence for the use of eptacog alfa for unexpected life-threatening bleeding in liver, cardiac or other surgery, or in blunt trauma, is not robust. In these circumstances, it should only be given as part of a clinical trial or in exceptional cases when other therapies have failed. The evidence for use of eptacog alfa in penetrating trauma is lacking. Conflicting RCT results exist for the prophylactic use of eptacog alfa in elective surgery; therefore, it cannot be recommended in this situation. There is insufficient evidence for a primary role of eptacog alfa in reversal of anticoagulation with heparin-like molecules and novel anticoagulant agents. There are effective therapies that correct all warfarin-induced factor deficiencies; thus, off-label use of eptacog alfa for reversal of warfarin should only be considered in the context of ICH. The evidence for eptacog alfa use in children is limited. The only RCT is in cardiac surgery for congenital heart disease, where eptacog alfa prophylaxis was actually associated with increased time to chest closure. It may be of potential benefit in some children with life-threatening bleeding in the context of trauma, surgery or liver disease (as additional therapy when surgical and/or medical control of bleeding has failed), but the overall benefit-risk ratio may be unfavourable if there is an underlying risk of thromboembolism (e.g. trauma, congenital heart disease, other hyperviscous or hypercoagulable states, presence of arterial or central venous catheters). Thromboembolism may be associated with eptacog alfa use. Although the magnitude of this risk and possible predisposing factors are not clearly delineated, some data suggest increased risk at higher doses. Variable effects of eptacog alfa use on mortality have been shown in a pooled analysis of RCTs. Data from some observational studies and postmarketing surveillance suggest an increased risk of thromboembolism associated with off-label uses. Further well designed studies are required to more definitively assess the risk of thromboembolism with eptacog alfa and to better determine its effects on mortality. Optimum dosages for nonhaemophiliac conditions are not defined and nor is the optimum timing of administration. Moreover, it is not clear which patients will be most likely to benefit in terms of haemostatic efficacy and mortality. In addition to conventional measures to stop bleeding (i.e. surgery and blood transfusion), correction of hypothermia and acidosis, and reversal of anticoagulation are all recommended. The outcomes (effectiveness and safety) of all off-label uses should be systematically evaluated and reported. Adequate data to assess cost effectiveness for eptacog alfa does not exist for most off-label indications.