Objectives: Base deficit (BD) and lactate are valuable screening tools for injured patients. They reflect the degree of oxygen debt and have been shown to predict outcome. Intake of ethanol and illicit drugs may further derange acid–base status. The authors evaluated the effect of blood alcohol level (BAL) and illicit drugs on admission BD and lactate levels in trauma patients.Methods: Prospective, observational study of trauma patients in a Level 1 trauma center. Patients with penetrating or blunt trauma were included in the study. Patients were further stratified into major or minor categories. Major was defined by an Injury Severity Score >15, blood transfusions, or a decrease in hematocrit of more than ten points. Injury categories were further divided into several subgroups based on presence or absence of ethanol (BAL ≥0.08 g/dL) or positive urine toxicology screen (Utox).Results: A total of 520 patients (84% male) with a mean (±SD) age of 33 (±15) years were studied. Compared with the minor injury categories, BD and lactate levels were significantly higher in the major injury categories in all different intoxication subgroups. Testing the diagnostic performance of BD and lactate in detecting major injury, the authors observed significant (p < 0.05) differences between the areas under the receiver operating characteristic curves for these two diagnostic tests compared with baseline in both intoxicated (BAL ≥0.08 g/dL and/or positive Utox) and nonintoxicated (BAL <0.08 g/dL and negative Utox) patients.Conclusions: The presence of ethanol and/or illicit drugs did not affect the ability of BD or lactate to identify patients with major injuries.