Presented herein is a rational program of prevention, diagnosis, and the surgical treatment of patients with the unintentional bile duct injuries. Examination results and surgical treatment of 1,117 patients, who underwent laparoscopic cholecystectomy for acute and chronic cholecystitis from 20052020, were studied. The criteria for inclusion in the study were difficult laparoscopic cholecystectomy (181 medical histories) and unintentional bile duct injuries resulting from laparoscopic cholecystectomy (95 patients). Laparoscopic cholecystectomy with a duration of 60 min was considered difficult. A total of 181 (17.7%) medical cases with difficult laparoscopic cholecystectomy and 95 patients with unintentional bile duct injuries were selected for this study. Instrumental studies were performed using X-ray contrast techniques such as: percutaneous fistulography, percutaneous-transhepatic, or intraoperative cholangiography, as well as relaparoscopy, ultrasound, endoscopic retrograde, or magnetic resonance cholangiopancreatography. A program approach to assist the patients with cholelithiasis was developed. Program implementation allows timely prevention and diagnosis of the unintentional bile duct injuries with minimal postoperative complications. The identification of the risk factors for difficult laparoscopic cholecystectomy indicates the need to comply with the preventive measures to prevent unintentional bile duct injuries and dictates the implementation of the surgical intervention by the most experienced surgeons from the second or third-level medical organizations. The rational option of surgical intervention aimed to eliminate the biliary tract injuries based on the following assessment criteria: general somatic condition of the patient, presence of the infectious complications, damage scale, crossed duct diameter, damage mechanism, and damage to the vessel. The right choice of the surgical intervention ensures a reduction in the number of complications and mortality, and quality of life improvement in patients with the unintentional bile duct injuries.