The quality of cold-stored livers declines with the extension of ischemic time and the risk of primary dys- or nonfunction increases. Here, we provide in vivo evidence for the efficacy of the previously developed end-ischemic gaseous oxygen persufflation technique to resuscitate liver grafts after extended storage times. Porcine livers were recovered according to standard multiorgan procurement protocol. Control livers were cold stored in histidine tryptophan ketoglutarate solution for 10 h (cold storage [CS]; n = 6) at 4°C. In the treatment group (n = 6), livers were additionally subjected to hypothermic reconditioning (HR) by gaseous oxygen persufflation via the caval vein for 2 h before transplantation. Viability was assessed by orthotopic liver transplantation and 1 week follow-up. HR significantly improved pretransplant energy charge and initial graft function after transplantation. One week survival after CS was 0% whereas five of six pigs (83%) survived in the HR group. At that time, coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts. Molecular analyses identify the prevention of ischemia-induced decline of cellular autophagy and mitigation of innate immune machinery (high-mobility group protein B1, interferon-β) as operative mechanisms among the protective effects provided by HR.