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Novel oral anticoagulant (NOAC) use is increasing in trauma patients. The reversal of these agents after hemorrhage is still evolving. The aim of our study was to evaluate outcomes after traumatic brain injury in patients on NOACs.3-year (2014–2016) analysis of our prospectively maintained traumatic brain injury (TBI) database. We included all TBI patients with intracranial hemorrhage (ICH) on anticoagulants. Patients were stratified into two groups, those on NOACs and on warfarin, and were matched in a 1:2 ratio using propensity score matching for demographics, injury and vital parameters, type, and size of ICH. Outcome measures were progression of ICH, mortality, skilled nursing facility (SNF) disposition, and hospital and intensive care unit (ICU) length of stay (LOS).We analyzed 1,459 TBI patients, of which 210 patients were matched (NAOCs, 70; warfarin, 140). Matched groups were similar in age (p = 0.21), mechanism of injury (p = 0.61), Glasgow Coma Scale (GCS) score (p = 0.54), Injury Severity Score (p = 0.62), and type and size of ICH (p = 0.09). Patients on preinjury NOACs had higher rate of progression (p = 0.03), neurosurgical intervention (p = 0.04), mortality (p = 0.04), and longer ICU LOS (p = 0.04) compared with patients on warfarin. However, there was no difference in hospital LOS (p = 0.22) and SNF disposition (p = 0.14). On sub-analysis of severe TBI patients (GCS ≤ 8), rate of progression (p = 0.59), neurosurgical intervention (p = 0.62), or mortality (p = 0.81) was similar in both groups.The use of NOACs generally carries a high risk of bleeding and can be detrimental in head injuries with ICH. NOAC use is associated with increased risk of progression of ICH, neurosurgical intervention, and mortality after a mild and moderate TBI. Primary care physicians and cardiologists need to reconsider the data on the need for anticoagulation and the type of agent used and weigh it against the risk of bleeding. In addition, development of reversal agents for the NOACs and implementation of a strict protocol for the reversal of these agents may lead to improved outcomes.Therapeutic studies, level III.