In the setting of acute brainstem herniation in traumatic brain injury (TBI), the use of hyperventilation to reduce intracranial pressure may be life-saving. However, undue use of hyperventilation is thought to increase the incidence of secondary brain injury through direct reduction of cerebral blood flow. This is a retrospective review determining the effect of prehospital hyperventilation on in-hospital mortality following severe TBI. All trauma patients admitted directly to a single level 1 trauma center from January 2000 to January 2007 with an initial Glasgow Coma Scale (GCS) score <or=8 were included in the study (n = 77). Patients without documented or with late (>20 min) arterial blood gas at presentation (n = 12) were excluded from the study. The remaining population (n = 65) was sorted into three groups based on the initial partial pressure of carbon dioxide: hypocarbic (Pco(2) < 35 mm Hg), normocarbic (Pco(2) 35-45 mm Hg), and hypercarbic (Pco(2) > 45 mm Hg). Outcome was based on mortality during hospital admission. Survival was found to be related to admission Pco(2) in head trauma patients requiring intubation (p = 0.045). Patients with normocarbia on presenting arterial blood gas testing had in-hospital mortality of 15%, significantly improved over patients presenting with hypocarbia (in-hospital mortality 77%) or hypercarbia (in-hospital mortality 61%). Although there are many reports of the negative impact of prophylactic hyperventilation following severe TBI, this modality is frequently utilized in the prehospital setting. Our results suggest that abnormal Pco(2) on presentation after severe head trauma is correlated with increased in-hospital mortality. We advocate normoventilation in the prehospital setting.