Xenotransplantation is a potential solution for the worldwide persisting donor organ shortage. However, immunological and physiological barriers need to be overcome before the first clinical trials can be started. Nonhuman primates are considered the most suitable recipients in preclinical xenotransplantation models. Heterotopic abdominal cardiac xenotransplantation is a well-established nonworking heart model for immunological and biological studies on acute and delayed xenograft rejection and xenograft survival. Nevertheless, orthotopic life-supporting pig-to-baboon heart transplantation is the only accepted model for future cardiac xenotransplantation in humans so far. Survival times of 3 months in at least 60% of consecutive experiments have to be achieved and a minimum number of ten nonhuman primates have to survive for this period of time before clinical transplantation may be started. We recently introduced the heterotopic thoracic technique of pig-to-baboon heart transplantation. We believe that this technique combines the advantages of a working heart model with the safety of heterotopic transplantation. We describe the technical procedure of the three different pig-to-baboon models and give detailed information on perioperative care of the recipients.