Introduction: The incidence of emergency department (ED) visits for Traumatic Brain Injury (TBI) in the United States exceeds 1,000,000 cases/year with the vast majority classified as mild (mTBI). Using existing computed tomography (CT) decision rules for selecting patients to be referred for CT, such as the New Orleans Criteria (NOC), approximately 70% of those scanned are found to have a negative CT. This study investigates the use of quantified brain electrical activity to assess its possible role in the initial screening of ED mTBI patients as compared to NOC. Methods: We studied 119 patients who reported to the ED with mTBI and received a CT. Using a hand-held electroencephalogram (EEG) acquisition device, we collected data from frontal leads to determine the likelihood of a positive CT. The brain electrical activity was processed off-line to generate an index (TBI-Index, biomarker). This index was previously derived using an independent population, and the value found to be sensitive for significant brain dysfunction in TBI patients. We compared this performance of the TBI-Index to the NOC for accuracy in prediction of positive CT findings. Results: Both the brain electrical activity TBI-Index and the NOC had sensitivities, at 94.7% and 92.1% respectively. The specificity of the TBI-Index was more than twice that of NOC, 49.4% and 23.5% respectively. The positive predictive value, negative predictive value and the positive likelihood ratio were better with the TBI-Index. When either the TBI-Index or the NOC are positive (combining both indices) the sensitivity to detect a positive CT increases to 97%. Conclusion: The hand-held EEG device with a limited frontal montage is applicable to the ED environment and its performance was superior to that obtained using the New Orleans criteria. This study suggests a possible role for an index of brain function based on EEG to aid in the acute assessment of mTBI patients.