Aim. To assess the effectiveness of preventive measures in endoscopic interventions on the major duodenal papilla.Methods. 1028 transpapillary interventions related to benign and malignant diseases were performed on 575 patients from 2007 to 2015. The analysis of complications rate and structure in different time intervals, taking into account the changing of patients management tactics and the use of different preventive technologies, was performed.Results. During 2007-2015, 30 cases of post-manipulational complications were registered (2.9% of patients) with a mortality rate of 0.09%. In the period from 2007 to 2008 post-manipulational complications rate was 8.5%. The main causes of complications were surgery long duration (up to 2 hours) and the lack of endoscopist experience. During this period, there was only one death, which was caused by acute cardiovascular insufficiency. From 2009 to 2011, the complications number decreased to 3.4% due to the careful patients selection for elective surgery, including the endosonography in diagnostic algorithm, octreotide, and hyoscine butylbromide use, the expansion of indications for the bile ducts stenting, exclusion the main pancreatic duct contrast, nasobiliary drainage in obstructive jaundice and suppurative cholangitis. In the period from 2012 to 2015, in the presence of a high risk of post-manipulational pancreatitis, every fifth intervention was completed by the main pancreatic duct stent placement with reducing of manipulations duration to 25-35 minutes, and increasing the surgery phases number. During this period, post-manipulational complications rate was 1.2%.Conclusion. Analysis of post-manipulational complications allowed to identify the most important measures to enhance the transpapillary interventions safety, thereby reducing the number of complications from 8.5% in the period of 2007-2008, to 1.2% in the period of 2014-2015.