Coagulopathy in patients with traumatic brain injury (TBI) is a well-studied concept. Prothrombin complex concentrate (PCC) has been shown to be an effective treatment modality for correction of TBI coagulopathy. However, its use and effectiveness compared with recombinant factor VII (rFVIIa) in TBI has not been established. The purpose of this study was to compare PCC and rFVIIa for the correction of TBI coagulopathy. All patients with a TBI and an induced or acquired coagulopathy whom received rFVIIa or PCC at our Level I trauma center during a 4-year period were reviewed. Data collected included demographics, changes in international normalized ratio and blood products transfusion, craniotomy rates, and time to neurosurgical intervention, thromboembolic complications, and mortality differences. The study was composed of 85 TBI patients, of whom 64 patients received PCC while 21 patients received rFVIIa. PCC group were more likely to be on coumadin (44% vs. 14%, p = 0.01). There was a significant decline in packed red blood cell transfusion and fresh frozen plasma after PCC administration (p < 0.01). There was no statistically significant difference in the craniotomy rate (28% vs. 10 %, p = 0.1) or the mean time to intervention between the two groups (201 [33] vs. 230 [10], p = 0.9). Mortality rates were lower in the PCC group compared with rFVIIa (67% vs. 47%, p = 0.02). Subsequent thromboembolic event was seen in one patient on rFVIIa. Mean cost of treatment per patient on PCC was $1,007 compared with $5,757 for rFVIIa (p < 0.01). PCC is safe and effective for treating coagulopathy in TBI patients, while reducing costs and resource use. PCC should be considered as an effective therapy to treat both acquired and induced coagulopathy in TBI with or without prehospital coumadin use. Therapeutic study, level IV.