Introduction: Anastomotic leak after pancreaticoduodenectomy is the most important cause of postoperative morbidity and mortality. Histological studies of bowel anastomoses have provided valuable insights regarding causes of anastomotic failure. However, this crucial information is lacking for pancreatico-enteric anastomoses. Methods: Pancreaticoduodenectomy was performed in a porcine model. Animals were survived up to 10 days and then the pancreatico-enteral anastomosis specimen was resected en bloc. Anastomotic bursting pressure was measured and histological sections of the anastomoses were examined. Results: Six out of 8 animals had excellent healing of the anastomoses. One animal developed a clinically significant leak at the pancreaticoduodenal anastomosis (12.5%) and one animal had a subclinical duodeno-duodenal leak discovered on necropsy (12.5%). Both anastomoses that failed had a collagen-to-tissue ratio less than 40%. In contrast, none of the anastomoses with a ratio greater than 40% showed any evidence of disruption. Conclusion: Our results indicate that quantitative measurement of collagen deposition at the pancreatic anastomosis provides objective assessment of healing of the pancreatic anastomosis. A survival porcine model of pancreaticoduodenectomy results in a similar leak rate to published data on pancreaticoduodenectomy in humans and will be useful for future studies assessing novel pharmacologic or technical interventions aimed at improving outcomes.