Background: Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. Methods: We studied seven consecutive patients aged 16-48 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33ΠC. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37ΠC. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. Findings: The four patients who were candidates for OLT were successfully maintained until transplantation with 13 h (range 10-14 h) of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49 mm Hg) and was reduced in all patients to 16