A need exists for an effective, safe bioartificial liver to support patients in fulminant hepatic failure (FHF). The purpose of this study was to determine the treatment efficacy of the novel gel-entrapment porcine hepatocyte bioartificial liver (BAL) in a fatal model of canine hepatic failure. FHF was produced in 27- to 30-kg halothane-anesthetized dogs by bolus infusion of the hepatotoxin d-galactosamine (d-Gal). Three groups were studied during the 48-hr experiment: Group d-Gal (n = 5) received galactosamine, 1.0 g/kg, iv at Time 0, Group HepBAL (n = 5) received d -Gal followed by continuous hemoperfusion with the BAL device loaded with ∼6 billion viable pig hepatocytes starting at Time 24 hr, and three dogs served as healthy controls (Group Control) and received up galactosamine. The primary endpoints were survival and coma development. Group d-Gal demonstrated 100% mortality from liver failure by 42 hr, characterized by a progressive rise in liver enzymes, total bilirubin, ammonia, and lactate and associated with coagulopathy, hypoglycemia, coma, and brain death. BAL therapy significantly delayed the onset of coma and improved survival (median 47 hr vs d -Gal median 36 hr). A significant delay in the rise of lactate and ammonia was also noted. BAL therapy prolonged survival and improved both laboratory and clinical markers of fatal liver failure. These data indicate that this BAL may have clinical utility in supporting human liver failure.