Background. Pancreatoduodenectomy is a radical surgical intervention in case of neoplasms of the pancreatoduodenal zone, which is accompanied by frequent postoperative complications. The critical point of the reconstructive stage of pancreatoduodenectomy is pancreaticojejunostomy (PES), which dictates the importance of improving the techniques of its repair and drainage, as well as the development of a differentiated approach to the choice of PES. The aim of the study: to evaluate the effectiveness of a differentiated approach to the choice of PES technique when performing pancreatoduodenectomy. Materials and methods. The study included 302 patients who underwent pancreatoduodenectomy for pancreatic neoplasms. The age of patients varied from 31 to 77 years, there were 178 (58.9 %) men, and 124 (41.1 %) women. In the comparison group (154 patients), a standard diagnostic and treatment algorithm was used with the choice of PES technique taking into account the intraoperative evaluation of the degree of the pancreatic parenchyma density and the assessment of the ductal system (surgeon’s experience and intuition). In the main group (148 patients), an improved diagnostic and treatment algorithm was used, which included non-invasive preoperative methods of visualization of changes in the pancreatic parenchyma, anatomical features of its isthmus and ductal system, as well as the use of developed methods for repair and drainage of the PES. Results. In the main group, the applied differentiated approach to the selection of PES consisted in the fact that at the preoperative stage, the degree of risk of developing pancreatic fistula (PF) was predicted: in 66 (44.6 %) patients, a low risk was detected, in 42 (28.4 %) — a moderate risk, 40 (27.0 %) people had a high risk. Identification of patients with a high risk of developing PF made it possible to carry out the necessary medical measures not only in the operating room, but also in the pre-operative stage, which affected a decrease in the frequency of severe forms of PF. Specifically, in the comparison group, type B was noted 2.5 times (χ2 = 3.94; p = 0.047) and type C — 6.4 times (p = 0.034 according to Fisher’s exact test) more often than in the main group. This became the basis for the development of PES techniques with plastic covering of the anastomotic zone and improvement of PES drainage techniques with simultaneous drainage of the biliodigestive anastomosis. The developed differentiated approach to the choice of PES method based on the preoperative assessment of the risk of PF made it possible to reduce the frequency of its development, especially severe forms (types B and C) from 16.2 % of cases in the comparison group to 5.4 % in main group (χ2 = 8.01; p = 0.005). Mortality due to pancreatic fistula in the main group was 0.7 %, in the comparison group — 4.8 % (p = 0.034, Fisher’s exact test). Conclusions. Carrying out a preoperative non-invasive assessment of the degree of changes in the pancreatic parenchyma and the state of the duct of Wirsung by means of fibroelastography and computer tomography made it possible to develop a differentiated approach to the choice of PES technique, taking into account the prediction of the risk of PF in the postoperative period (sensitivity — 90.5 %, specificity — 81, 8 %, diagnostic accuracy — 86.1 %). The use of the developed methods with a falciform ligament wrap and cholangiodrainage to drain PES in soft pancreas made it possible to reduce in half the frequency of PF development (p < 0.05), which led to a decrease in mortality by almost 7 times (p < 0.05).