The aim of this study was to develop a porcine model of post-operative liver failure (POLF) that could accurately reproduce all the neurological and metabolic parameters of the corresponding clinical syndrome that may develop after extensive liver resections.In our model, we induced POLF by combining extended left hepatectomy and ischemia of the small liver remnant of 150 min duration. Subsequently, the remnant liver parenchyma was reperfused and the animals were closely monitored for 24 h.Twelve Landrace pigs (weight 25-30 kg) were randomly assigned in two groups; eight of them constituted the experimental group, in which POLF was induced (POLF group, n = 8), whereas the rest of them (n = 4) were included in the control group (sham laparotomy without establishment of POLF). RESULTS (MEANS ± SD): All POLF animals gradually developed neurological and biochemical signs of liver failure including, among many other parameters, elevated intracranial pressure (24.00 ± 4.69 versus 10.17 ± 0.75, P = 0.004) and ammonia levels (633.00 ± 252.21 versus 51.50 ± 9.49, P = 0.004) compared with controls. Histopathologic evaluation of the liver at the end of the experiment demonstrated diffuse coagulative necrosis and severe architectural distortion of the hepatic parenchyma in all POLF animals.Our surgical technique creates a reproducible porcine model of POLF which can be used to study the pathophysiology and possible therapeutic interventions in this serious complication of extensive hepatectomies.