Abstract: Objective To analyze the influence of difficult cholecystectomy (DC) on intraoperative and postoperative complications and to explore risk factors of DC, so as to establish a risk prediction model of DC. Methods Data of 201 patients who underwent cholecystectomy from January 1, 2018 to November 10, 2019 were analyzed retrospectively. The highest quartile (P75) of cholecystectomy operation time was used as a cutting point of DC (≥P75) and NLC (＜P75). Logistic regression was used to analyze the influencing factors of DC, and its risk model was constructed for prediction. Results A total of 201 patients were included, 53 were in DC group (including 3 cases of conversion to laparotomy) and 148 were in NLC group (all by laparoscope). The intraoperative blood loss, the frequency of vomiting at the first 24-hour after operation, the rates of conversion to abdominal surgery and drainage tube placement were higher in DC group than those of NLC group (P＜0.01). The time of the first anal exhaust and length of hospital stay were longer in DC group than those of NLC group (P＜0.05). The multivariate Logistic regression analysis showed that body mass index (BMI) ＞ 25 kg/m2, white blood cell (WBC) count ＞ 10×109/L, calculus incarcerated in neck of gallbladder, the relapse of acute cholecystitis in the last 2 months ＞ 4 times, thickness of gallbladder wall ＞ 0.5 cm and maximum diameter of stone ＞ 2 cm were independent risk factors for DC. The prediction efficiency of the Logistic regression equation was 0.879 (χ2=1.457，P＞0.05). Conclusion The difficult cholecystectomy can increase the risk of intraoperative and postoperative complications. The establishment of a risk prediction model has a certain clinical guiding value for difficult cholecystectomy.