Hemorrhagic shock in the setting of traumatic brain injury (TBI) reduces cerebral blood flow and doubles mortality. The optimal resuscitation strategy for hemorrhage in the setting of TBI is unknown. We hypothesized that, among patients presenting with concomitant hemorrhagic shock and TBI, resuscitation including whole blood (WB) is associated with decreased overall and TBI-related mortality when compared with patients receiving component (COMP) therapy alone.