The aim of this study was to explore the effects of barbiturate coma on cerebral tissue oxygen tension and cerebrovascular pressure reactivity (PRx), as an index of cerebral autoregulation in severe head injury patients. This was a prospective observational clinical study of 12 patients with severe traumatic brain injury, carried out at a tertiary-level neurosurgical intensive care unit between April 2002 and May 2005. All patients received standard neurosurgical intensive care and monitoring. Probes for intracranial pressure (ICP), brain temperature (BT) and brain tissue oxygenation (PTiO2) were inserted into (noncontused) normal-looking white matter. Cerebrovascular PRx was measured as a moving correlation between ICP and arterial blood pressure. Barbiturate coma was instituted when ICP became refractory (ICP>20 mmHg). All data from the multimodal monitoring were digitally extracted and statistically analysed. The mean ICP decreased with barbiturate coma in eight of the 12 patients (75% of the patients), but only four achieved a value below 20 mmHg. Of eight patients with prebarbiturate PTiO2 levels above 10 mmHg, six had a further improvement in oxygenation. Thus, concordant favourable changes in ICP, PRx and PTiO2 with barbiturate coma were seen in those who survived. Effective response to barbiturates can be detected by improved PTiO2 and autoregulation (PRx) in severe head injury patients.