Porcine livers have the potential to support liver function via extracorporeal liver cross-circulation (ELC) until recovery or transplantation. To assess the functional integrity of both native human and porcine livers during ELC, we used the clearance of intravenously administered 13C-cholate to probe effective hepatic perfusion in 4 decedents maintained on ELC for 72 to 102 hours. Genetically modified porcine livers (EGEN-5784) were perfused using the OrganOx metra-ELC device. Hepatic filtration rate was calculated for the native human liver and the EGEN-5784 liver in ELC. During ELC, total hepatic filtration rate increased substantially compared with pre-ELC values, exceeded the upper limit of the normal range, and remained stable throughout the ELC period. Simultaneous measurement of cholate clearance in human and porcine livers during ELC provides real-time assessment of each organ’s functional contribution and may inform decisions regarding optimal ELC duration, timing of disconnection, and necessity of liver transplantation.