Early and accurate diagnosis and prognosis of patients with fulminant liver failure is of critical importance for optimum management. We investigated the role of transjugular liver biopsy in the management of patients with fulminant liver failure and assessed its value in comparison with the recently proposed King's College criteria. Sixty-one patients with fulminant liver failure, ages 2 to 82 yr, were retrospectively analyzed. The main outcome measures were survival vs. death or progression to orthotopic liver transplantation. Transjugular liver biopsy was successful in 60 of 61 patients, with a mean core tissue length of 2.1 cm. There were eight minor complications, all of which were managed conservatively. Biopsy specimens were evaluated for degree of fibrosis, percentage of hepatocellular necrosis and presence of bile duct proliferation, hepatocellular mitotic figures and binucleate hepatocytes for each of the 54 specimens available for analysis. In 34 of 54 patients (63%), the presumed clinical diagnosis was confirmed by transjugular liver biopsy. In 11 patients the procedure served to clarify clinical uncertainty, whereas in 9 of 54 (16.7%) the diagnosis was altered after transjugular liver biopsy. The percentage of necrosis was the only histological parameter that appeared to have significant discriminatory prognostic value, with only 2 of 19 survivors having greater than 70% necrosis. Twenty-one of these biopsy specimens were reviewed by two pathologists, and their degree of correlation for the various features was assessed. Almost perfect concordance was found between the two pathologists on the percentage of hepatocellular necrosis. The King's College criteria correctly identified outcome in 100% of patients with acetaminophen-induced fulminant liver failure and in 91% of nonsurvivors and 82% of survivors with nonacetaminophen-induced fulminant liver failure. In six of eight nonsurvivors and two survivors with nonacetaminophen-induced fulminant liver failure, in whom the King's College criteria were inconclusive, the percentage of necrosis correctly predicted the outcome. These results indicate that transjugular liver biopsy is both safe and effective as an adjuvant to the King's College criteria in the diagnosis and prognosis of patients with nonacetaminophen-induced fulminant liver failure. (HEPATOLOGY 1993;18:1370–1374.)