Xenotransplantation (XTx) is an increasingly realistic solution to the organ shortage. Clinical XTx may require off-site procurement in a designated pathogen free (DPF) facility necessitating a period of cold ischemic time during transportation. This study evaluates the impact of different kidney preservation strategies on early graft function in pig-to-baboon XTx in a series of eight cases of pig-to-baboon xenotransplantation performed after five hours of cold ischemic time and compares these results to six cases of pig-to-baboon xenotransplantation performed with minimal ischemic time. Our data indicates that porcine kidneys appear to be particularly sensitive to IRI after cold preservation, especially across xenogeneic barriers, and routine static cold storage leads to hyperacute graft loss even in recipients with low levels of preformed antibodies. Hypothermic machine perfusion minimizes IRI and may prevent early xenograft loss.