BACKGROUND: During orthotopic liver transplantation (OLT) for acute liver failure (ALF), some patients develop acute increases in intracranial pressure (ICP). The authors tested the hypothesis that increases in ICP during OLT for ALF can be prevented by moderate hypothermia. METHODS: Sixteen patients with ALF undergoing OLT were studied. Depending on the measured ICP before OLT, the patients were divided into three groups as follows: group I (n=6), did not require treatment for increased ICP (ICP <15 mm Hg); group II (n=5), had episodes of increased ICP that were controlled by conventional treatment (group I and group II patients were maintained normothermic during OLT); and group III (n=5), had uncontrolled increased ICP before OLT for which they had been cooled and underwent OLT with the median core temperature of 33.4 degrees C (92.1 degrees F) (range, 31.9 degrees -33.8 degrees C [89.4 degrees -92.8 degrees F]) RESULTS: There was a significant increase in ICP during the dissection and reperfusion phases in the patients in groups I and II (P=0.004 and P=0.006, respectively). Patients in group III had no significant increase in ICP during the OLT. The increase in ICP in groups I and II was associated with an increase in cerebral blood flow, which was not observed in group III. The increase in ICP was corrected during the anhepatic phase of the operation. There was no difference in the requirement of transfusions or incidence of postoperative infection between the groups. CONCLUSIONS: Moderate hypothermia is safe and successfully prevents increases in ICP during OLT for ALF.