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Intracranial hypertension after severe head injury is associated with case fatality, but there is no sound evidence that monitoring of intracranial pressure (ICP) and targeted management of cerebral perfusion pressure (CPP) improve outcome, despite widespread recommendation by experts in the field. The purpose was to determine the effect of ICP/CPP-targeted intensive care on functional outcome and therapy intensity levels after severe head injury.Retrospective cohort study with prospective assessment of outcome.Two level I trauma centers in The Netherlands from 1996 to 2001.Three hundred thirty-three patients who had survived and remained comatose for >24 hrs, from a total of 685 consecutive severely head-injured adults.In center A (supportive intensive care), mean arterial pressure was maintained at approximately 90 mm Hg, and therapeutic interventions were based on clinical observations and computed tomography findings. In center B (ICP/CPP-targeted intensive care), management was aimed at maintaining ICP <20 mm Hg and CPP >70 mm Hg. Allocation to either trauma center was solely based on the site of the accident.We measured extended Glasgow Outcome Scale after ≥12 months. Patient characteristics were well balanced between the centers. ICP monitoring was used in zero of 122 (0%) and 142 of 211 (67%) patients in centers A and B, respectively. In-hospital mortality rate was 41 (34%) vs. 69 (33%; p = .87). The odds ratio for a more favorable functional outcome following ICP/CPP-targeted therapy was 0.95 (95% confidence interval, 0.62–1.44). This result remained after adjustment for potential confounders. Sedatives, vasopressors, mannitol, and barbiturates were much more frequently used in center B (all p < .01). The median number of days on ventilator support in survivors was 5 (25th–75th percentile, 2–9) in center A vs. 12 (7–19) in center B (p < .001).ICP/CPP-targeted intensive care results in prolonged mechanical ventilation and increased levels of therapy intensity, without evidence for improved outcome in patients who survive beyond 24 hrs following severe head injury.