The aim of this study was to determine the impact of ethanol (ETOH) on the incidence of severe traumatic brain injury (sTBI)-associated coagulopathy and to examine the effect of ETOH on in-hospital outcomes in patients sustaining sTBI. Patients admitted to the surgical intensive care unit from June 2005 through December 2008 following sTBI, defined as a head Abbreviated Injury Scale (AIS) score ≥3, were retrospectively identified. Patients with a chest, abdomen, or extremity AIS score >3 were excluded to minimize the impact of extracranial injuries. Criteria for sTBI-associated coagulopathy included thrombocytopenia and/or elevated International Normalized Ratio (INR) and/or prolonged activated partial thromboplastin time (aPTT). The incidence of admission coagulopathy, in-hospital complications, and mortality were compared between patients who were ETOH positive [ETOH (+)] and ETOH negative [ETOH (-)]. During the study period, there were 439 patients with ETOH levels available for analysis. Overall, 46.5% (n=204) of these patients were ETOH (+), while 53.5% (n=235) were ETOH (-). Coagulopathy was significantly less frequent in the ETOH (+) patients compared to their ETOH (-) counterparts (5.4% versus 15.3%; adjusted p<0.001). In the forward logistic regression analysis, a positive ETOH level proved to be an independent protective factor for admission coagulopathy [OR (95% CI)=0.24 (0.10,0.54; p=0.001]. ETOH (+) patients had a significantly lower in-hospital mortality rate than ETOH (-) patients [9.8% versus 16.6%; adjusted p=0.011; adjusted OR (95% CI)=0.39 (0.19,0.81)]. For brain-injured patients arriving alive to the hospital, ETOH intoxication is associated with a significantly lower incidence of early coagulopathy and in-hospital mortality. Further research to establish the pathophysiologic mechanisms underlying any potential beneficial effect of ETOH on the coagulation system following sTBI is warranted.