Liver tumors located near the retrohepatic vena cava are often considered nonresectable. For these patients cryoablation could be a therapeutic option. In this study the safety and efficacy of hepatic cryosurgery involving the retrohepatic vena cava were investigated. Cryolesions involving the vena cava were created in 26 pigs. Follow-up was 24 h and 14 days. The extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. The cyronecrosis extended into the wall of the vena cava in 81% of the animals. All animals had an uneventful recovery without any complications such as ruptures of the vessel, thrombosis or pulmonary embolism. Microscopically elastic and collagenous fibers of the cava wall remained intact. The continuity of the vessel wall was conserved. In conclusion, the safety and efficacy of cryosurgical treatment involving the retrohepatic vena cava were shown in a pig model.