Background Identifying patients who may progress to a poor clinical outcome will encourage earlier appropriate therapeutic interventions. Brain edema may contribute to secondary injury in traumatic brain injury (TBI) and thus, may be a useful prognostic indicator. Objective We determined whether the presence of brain edema on the initial computed tomography (CT) scan of TBI patients would predict poor in-hospital outcome. Methods We performed a retrospective review of all trauma patients with nonpenetrating head trauma at a Level I Trauma Center. International Classification of Diseases, Ninth Revision codes indicated the presence of brain edema and we evaluated the validity of this pragmatic assessment quantitatively in a random subset of patients. In-hospital mortality was the primary outcome variable. Univariate analysis and logistic regression identified predictors of mortality in all TBI patients and those with mild TBI. Results Over 7200 patients were included in the study, including 6225 with mild TBI. Measurements of gray and white matter CT density verified radiological assessments of brain edema. Patients with documented brain edema had a mortality rate over 10 times that of the entire study population. With logistic regression accounting for Injury Severity Score, Glasgow Coma Scale score, other CT findings, and clinical variables, brain edema predicted an eightfold greater mortality rate in all patients (odds ratio 8.0, 95% confidence interval 4.6–14.0) and fivefold greater mortality rate for mild TBI patients (odds ratio 4.9, 95% confidence interval 2.0–11.7). Conclusions Brain edema is an independent prognostic variable across all categories of TBI severity. By alerting emergency physicians to patients with poor predicted clinical outcomes, this finding will drive better resource allocation, earlier intervention, and reduced patient mortality.