The aim of the study was to evaluate the validity of the Sport Concussion Assessment Tool-Second Edition (SCAT2) in patients with acute mild traumatic brain injuries (mTBIs) in a civilian trauma setting. In addition, the SCAT2 was compared to the Military Acute Concussion Evaluation (MACE). All the participants of the study were prospectively recruited from the emergency department of Tampere University Hospital (Tampere, Finland). Patients (n=49) between the ages of 18 and 60 years, with no premorbid medical or psychiatric conditions, who met the World Health Organization criteria for mTBI, were enrolled. Trauma controls (n=33) were recruited using similar study criteria. The main measures of the study consisted of SCAT2, MACE, and mTBI severity markers, including neuroimaging (computed tomography and conventional magnetic resonance imaging [MRI]), and 1-month clinical outcomes (postconcussion syndrome diagnosis and return to work status). The scoreable components of the SCAT2 performed variably across five dimensions of validity (diagnostic, criterion, divergent, predictive, and responsiveness). The Standardized Assessment of Concussion component reasonably discriminated mTBI patients from controls, was associated with MRI lesions, improved over time, and predicted return to work. Symptom scores differentiated patients with mTBIs from controls, and elevated initial symptom scores in patients with mTBI were associated with a greater risk of persistent postconcussion symptoms. The SCAT2 was superior to the MACE. The SCAT2 appears useful for detecting acute mTBI-related symptoms and cognitive impairment, refining prognosis, and monitoring recovery.