Recent studies have suggested that moderate doses of ethanol (ETOH) before traumatic brain injury (TBI) may have a neuroprotective role. : The objective of this study is to investigate the effects of serum ETOH levels on outcomes after TBI. Our hypothesis was that ETOH exposure is associated with improved survival in severe TBI patients and that the serum ETOH levels on admission correlate with survival. All patients sustaining severe TBI (head abbreviated injury score >or=3) admitted to the Surgical Intensive Care Unit at the Los Angeles County + University of Southern California Medical Center from January 2000 to December 2005 who had a serum ETOH level measured on admission were analyzed. Patients were classified into ETOH-positive and ETOH-negative groups, according to the serum ETOH levels and compared for differences in outcomes using logistic regression to adjust for clinically and statistically relevant confounding factors. During the 5-year study period, 482 severe TBI patients admitted to the Surgical Intensive Care Unit at Los Angeles County + University of Southern California Medical Center had a serum ETOH level measured on admission. A total of 47% of severe TBI patients were tested for ETOH. ETOH levels were positive in 37% (179) and negative in 63% (303) of the TBI patients. The ETOH-positive group had a higher percentage of males (91% vs. 79%, p = 0.001), lower percentage of penetrating injuries (9% vs. 20%, p = 0.002), and lower injury severity score (25.7 +/- 11.5 vs. 28.4 +/- 14.1, p = 0.05). Overall mortality was significantly lower in the ETOH-positive group at 27% versus 40% (odds ratio = 0.55, 95% confidence interval: 0.37-0.82; p = 0.004). This survival benefit remained significant after multivariable analysis (adjusted odds ratio = 0.54, 95% confidence interval: 0.31-0.92; adjusted p = 0.02). The mean serum ETOH level was significantly higher for survivors than for nonsurvivors (0.11 +/- 0.21 vs. 0.05 +/- 0.10, p < 0.001). The serum ETOH levels significantly correlated with the probability of survival (r = 0.21, p < 0.001), but this correlation was not strong as shown by the low r value. The results of this study suggest that elevated ETOH serum levels are independently associated with higher survival in patients with severe traumatic brain injuries. Additional research is required to further investigate the mechanism and potential therapeutic implications of this association.