Pancreatico-jejunal anastomosis still represents the main source of postoperative complications after pancreatoduodenectomy. In this study our experience on the occlusion of the residual pancreatic stump instead of pancreatico-jejunal anastomosis is reviewed. Between March 1981 and December 1995 we performed 223 pancreatoduodenectomies using Neoprene injection into the Wirsung duct for pancreatic carcinoma of the head (123 cases), ampullary carcinoma (36 cases), distal bile duct cancer (23 cases), islet cells carcinoma (17 cases), chronic pancreatitis (11 cases), duodenal carcinoma (5 cases), miscellaneous diseases (8 cases). Neoprene is a fluid, synthetic glue which polymerized and hardens when in contact with the pancreatic juice, inducing a fibrosis tissue which spares the endocrine component. We observed a 4.9% operative mortality (11 patients): 5 abdominal sepsis, 1 DIC, 1 aortoiliac thrombosis, 1 pulmonary embolism, 1 stroke, 1 hepatic failure, 1 cardiac failure. Overall morbidity was 44.8% (100 patients): in 25 cases (11.2%) a major complication requiring reintervention occurred. In 38 patients (17%) pancreatic fistula was detected: median duration was 43 days, with a mean output of 5.3 ml/day; in all cases a spontaneous solution of the fistula was observed. In conclusion, intraductal injection of Neoprene after pancreatoduodenectomy is a safe procedure, it represents an useful alternative to pancreatico-jejunal anastomosis.