Facial graft transplantation remains the operation of choice for patients with extensive tissue defects in the maxillofacial region. This study aimed to set up an experiment on biological objects, develop and test a combined facial graft cross-transplantation technique, select the anesthetic aid allowing to reduce the risks of perioperative complications, improve survivability of the subjects by reducing the duration of surgical intervention, develop a postoperative therapy and rehabilitation protocol, assess detection of an acute rejection reaction and develop the immunosuppressive therapy protocol. We conducted three series of facial graft transplantation surgeries on 26 minipigs and tested the typical component combinations and flap designs. At all stages of the experiment, we managed to have the subjects surviving for over 30 days without disrupting their vital functions. The immunosuppression procedure was developed and tested. The chosen technique allows transplanting two grafts within a single surgery on one pair.