BACKGROUND: Important differences with respect to gender exist in the prognosis and mortality of traumatic brain injury (TBI) patients. The objective of this study was to assess the role of gender as an independent factor in cerebral oxygenation variations following red blood cell transfusion (RBCT). METHODS: This retrospective analysis of a prospective study was conducted on patients with severe TBI. Hemoglobin levels were measured at baseline and 6 h after transfusion. Brain tissue oxygen pressure (PbrO(2)), cerebral perfusion pressure (CPP), intracranial pressure (ICP), and mean arterial pressure (MAP) were measured at baseline, at the end of RBCT and at 1, 2, 3, 4, 5, and 6 h after transfusion. After the patients were stratified into two groups according to gender, the effect of RBCT on PbrO(2) (cerebral oxygenation) was analyzed using a multivariate analysis of variance with repeated measures (MANOVA). The MANOVA was repeated after adjusting for all covariables with baseline differences between groups. RESULTS: At baseline, we found differences in age (P = 0.01), weight (P = 0.03), MAP (P = 0.01), ISS (P = 0.05), and CCP (P = 0.01) between the groups. After adjusting for these co-variables, we observed that gender and age were related to the increase in PbrO(2) (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: Our results suggest that the effect of RBCT on cerebral oxygenation, as measured by PbrO(2), is greater in women than in men.