AIM To examine whether thermo-perfusion of the bile duct and duodenum may protect these organs during cryoablation of adjacent pancreatic tissue. STUDY DESIGN Cryoablation of the pancreatic tissue, adjacent to the common bile duct and duodenum was performed in two groups of pigs. In the experimental group, the bile duct and duodenum were protected during the cryo-procedure by intraluminal perfusion of warm saline. In the control group, cryoablation was performed without thermo-protection. RESULTS All three animals in the control group developed duodenal perforation and abscesses and died within a week. All the pigs in the experimental group survived and on re-operation 14 days after the first procedure were found to have normal duodenum and bile duct adjacent to the cryoablated pancreatic tissue. Histological examinations confirmed these results. CONCLUSION The present study confirms the feasibility and efficacy of thermo-protection of the duodenum and common bile duct during cryoablation of the head of the pancreas.