Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.