Background: To investigate the safety and feasibility of a new intrahepatic cholangiojejunostomy for multiple intrahepatic biliary ductal openings after hepatobiliary resection. Materials and methods: Forty-eight pigs were randomly assigned into two groups: the new intrahepatic cholangiojejunostomy group (n = 24); and the control group (n = 24) with classical hepaticojejunostomy. Six pigs in each group were sacrificed on postoperative day 7, 30, 90 and 180. The primary outcomes were postoperative mortality, morbidity, and the pathological changes in the anastomoses. The secondary outcomes were levels of aspartate transaminase, bilirubin, albumin and alkaline phosphate. Results: The operations were successfully carried out. The rates of anastomotic leakage and cholangitis in the study group were 0% and 8.3% (2/24), while in the control group they were 4.2% (1/24) and 20.8% (5/24), respectively. The stenotic rates of the sectional areas of the anastomotic stomas in the study group were lower than those in the control group on postoperative day 7, 30, 90 and 180 (p < 0.001, p = 0.002, p < 0.001, and p = 0.001, respectively). Under microscopy, in the study group, the anterior wall of the stoma was everted and sunken while the posterior wall was protruded in a semicircular-disc shaped. The liver transection plane was epithelialized with mucosal covering by post-operative day 30. In the control group, however, the stoma was centripetally protruded with a relative circular stenosis. Conclusions: The new intrahepatic cholangiojejunostomy is safe, simple, and convenient for multiple biliary ductal openings. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.