Objective: To comparatively assess outcome of patients undergoing monitoring and management of cerebral extraction of oxygen along with cerebral perfusion pressure vs. outcome of patients undergoing monitoring and management of cerebral perfusion pressure alone in severe acute brain trauma. Design: Prospective, interventional study. Setting: Intensive care unit of a university hospital. Patients: Adults (n = 353) with severe acute brain trauma. A group of 178 patients underwent continuous monitoring and management of cerebral extraction of oxygen and cerebral perfusion pressure, while a control group of 175 patients underwent monitoring and management of cerebral perfusion pressure only. Interventions: Routine neuroemergency procedures. Measurements and Main Results: The two groups of patients were matched with regard to age, postresuscitation Glasgow Coma Scale scores, rates of acute surgical intracranial hematomas and brain swelling, pupillary abnormalities, early hypotensive events (before intensive care monitoring), as well as initial levels of intracranial pressure and cerebral perfusion pressure. Outcome at 6 months post injury was significantly better (p<.00005) in the 178 patients undergoing monitoring and management of cerebral extraction of oxygen along with cerebral perfusion pressure, than in the control group of 175 patients undergoing monitoring and management of cerebral perfusion pressure alone. Conclusion: In patients with severe acute brain trauma and intracranial hypertension associated with compromised cerebrospinal fluid spaces, monitoring and managing cerebral extraction of oxygen in conjunction with cerebral perfusion pressure result in better outcome than when cerebral perfusion pressure is managed alone.