Although recent evidence suggests a beneficial effect of alcohol for patients with traumatic brain injury (TBI), the level of alcohol that confers the protective effect is unknown. Our objective was to investigate the relationship between admission blood alcohol concentration (BAC) and outcomes in patients with isolated moderate to severe TBI. From 2005 to 2009, the Los Angeles County Trauma Database was queried for all patients ≥14 years of age with isolated moderate to severe TBI and admission serum alcohol levels. Patients were then stratified into four levels based on admission BAC: None (0 mg/dL), low (0-100 mg/dL), moderate (100-230 mg/dL), and high (≥230 mg/dL). Demographics, patient characteristics, and outcomes were compared across levels. In evaluating 3794 patients, the mortality rate decreased with increasing BAC levels (linear trend P < 0.0001). In determining the relationship between BAC and mortality, multivariable logistic regression analysis demonstrated a high BAC level was significantly protective (adjusted odds ratio 0.55; 95% confidence interval: 0.38-0.8; P = 0.002). In the largest study to date, a high (≥230 mg/dL) admission BAC was independently associated with improved survival in patients with isolated moderate to severe TBI. Additional research is warranted to investigate the potential therapeutic implications.