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Trauma-related hypotension and coagulopathy worsen secondary brain injury in patients with traumatic brain injuries (TBIs). Early damage control resuscitation with blood products may mitigate hypotension and coagulopathy. Preliminary data suggest resuscitation with plasma in large animals improves neurologic function after TBI; however, data in humans are lacking.We retrospectively identified all patients with multiple injuries age >15 years with head injuries undergoing prehospital resuscitation with blood products at a single Level I trauma center from January 2002 to December 2013. Inclusion criteria were prehospital resuscitation with either packed red blood cells (pRBCs) or thawed plasma as sole colloid resuscitation. Patients who died in hospital and those using anticoagulants were excluded. Primary outcomes were Glasgow Outcomes Score Extended (GOSE) and Disability Rating Score (DRS) at dismissal and during follow-up.Of 76 patients meeting inclusion criteria, 53% (n = 40) received prehospital pRBCs and 47% (n = 36) received thawed plasma. Age, gender, injury severity or TBI severity, arrival laboratory values, and number of prehospital units were similar (all p > 0.05). Patients who received thawed plasma had an improved neurologic outcome compared to those receiving pRBCs (median GOSE 7 [7–8] vs. 5.5 [3–7], p < 0.001). Additionally, patients who received thawed plasma had improved functionality compared to pRBCs (median DRS 2 [1–3.5] vs. 9 [3–13], p < 0.001). Calculated GOSE and DRS scores during follow-up, median 6 [5–7] months, demonstrated increased function in those resuscitated with thawed plasma compared to pRBCs by both median GOSE (8 [7–8] vs. 6 [6–7], p < 0.001) and DRS (0 [0–1] vs. 4 [2–8], p < 0.001).In critically injured trauma patients with TBI, early resuscitation with thawed plasma is associated with improved neurologic and functional outcomes at discharge and during follow-up compared to pRBCs alone. These preliminary data support the further investigation and use of plasma in the resuscitation of critically injured TBI patients.Therapeutic, level V.