BackgroundA post-operative pancreatic fistula is a major cause of morbidity and mortality in patients undergoing pancreaticoduodenectomy. We compared two methods of reconstruction of pancreaticojejunal anastomosis, an isolated loop with a single loop, to assess their effects on the incidence and severity of fistula. MethodsThe data was collected in an ambispective manner. The drain fluid was sent for amylase measurement on post-operative day 3 and a fistula was defined and classified according to the 2016 modification of the International Study Group for Pancreatic Surgery definition. The patients were divided into the isolated (Group I) and single (Group II) loop groups and compared for the incidence and severity of clinically relevant fistula along with other parameters. ResultsA total of 349 (Group I: 201, Group II: 148) patients were included in the study. The incidence of clinically relevant fistula was comparable (p = 0.206). Grade C fistula was found to be lower in the group I (7 % vs 11.6 %, p = 0.137), in patients with a soft pancreas (8.5 % vs 18.3 %, p = 0.049) and pancreatic duct diameter less than 5 mm (9.8 % vs 17.2 %, p = 0.036). The operative time was lower in Group I than in Group II (438 min vs 478, p < 0.001). ConclusionWe found that the incidence of clinically relevant fistula was similar in both the groups but the isolated reconstruction method reduced the incidence of severe fistula. In patients with a smaller pancreatic duct, soft pancreas echotexture and obesity, it provides a safer alternative and can be performed in less time than a single loop reconstruction.