To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.