Until now, the management of the acute haemorrhagic episodes as intracerebral hematomas in severe haemophilia A with high titres of inhibitors to FVIII:C (>100 BU/ml) and porcine FVIII:C cross reactivity remains a very difficult challenge for medical teams. In fact, in order to perform neuro-surgical procedures to remove the intracerebral hematoma when it is urgently needed, the immediate care of these patients pursues the careful choice of alternative therapies. In this attending phase, on the basis of our experience, the current by-passing clotting factors, as activated prothrombin complex concentrates (APCC), may be employed together with infusion of high doses of tranexamic acid. We have applied the following protocol to treat three patients with SNC haemorrhage: hospitalization, bed rest, following of cephalematomas by computed scan tomography twice a week, APCC (FEIBA TIM 3, Immuno, Pisa) at a dosage of 40 IU/kg every 12 h, tranexamic acid (150 mg/kg/day) infusion and oral chlorpromazine (150 mg/day) for the first decade. Further this treatment was reduced when a progressive improvement of the cerebral haemorrhages was observed. Haemostasis was always achieved but the duration of therapy needed varied widely until the fourth week (FEIBA, 2000 IU/day). As expected, aPTT was not shortened and inhibitor plasma levels to human FVIII:C remained high, as the basal ones. Parameters for coagulation activation, thrombin-ATIII complexes (TAT) (ELISA, Behring) and prothrombin fragment F1+2 (ELISA Behring) did incrase slightly with a rise in fibrin degradation products (FDP, latex agglutination test, Boehringer Mannheim) and fibrinopeptide A (FPA ELISA, Stago). Platelet count decreased to a minimum of 101,000μl only in one patient. All patients well recovered after one month. Last CT scan demonstrated the complete resolution of the cerebral hemorrhage. From our observations, we suggest that FEIBA replacement therapy would be a safe and efficacious choice to treat SNC haemorrhage in haemophilia A with high inhibitor levels to human FVIII:C.