OBJECTIVE To evaluate the concept of a cerebrovascular pressure reactivity-guided optimal cerebral perfusion pressure after traumatic brain injury by analyzing the relationship between optimal cerebral perfusion pressure and brain tissue oxygen. METHODS Prospective observational cohort study. METHODS Neurosurgical intensive care unit of a university hospital. METHODS Thirty-eight patients after head injury. METHODS Continuous computerized monitoring of mean arterial pressure, intracranial pressure, and brain tissue oxygen for 5.3 +/- 2.6 days. The index of cerebrovascular pressure reactivity was calculated as a moving correlation coefficient between spontaneous low-frequency fluctuations of mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure was defined as the cerebral perfusion pressure level with the lowest average index of cerebrovascular pressure reactivity. RESULTS Optimal cerebral perfusion pressure could be identified in 32 of 38 patients. Median optimal cerebral perfusion pressure was between 70 and 75 mm Hg (range, 60-100 mm Hg). Below the level of optimal cerebral perfusion pressure, brain tissue oxygen decreased in parallel to cerebral perfusion pressure, whereas brain tissue oxygen reached a plateau above optimal cerebral perfusion pressure. Optimal cerebral perfusion pressure correlated significantly with the cerebral perfusion pressure level, where brain tissue oxygen reached its plateau (r = .79; p < .01). Average brain tissue oxygen at optimal cerebral perfusion pressure was 24.5 +/- 6.0 mm Hg. CONCLUSIONS This study supports the concept of cerebrovascular pressure reactivity-based individual optimal cerebral perfusion pressure. Driving cerebral perfusion pressure in excess of optimal cerebral perfusion pressure does not yield improvements in brain tissue oxygen after head injury and should be avoided, whereas cerebral perfusion pressure below optimal cerebral perfusion pressure may result in secondary cerebral ischemia.