Objective To investigate the quality of life (QoL) in elderly patients with gallstones after cholecystectomy and its influencing factors. Methods A retrospective analysis was conducted of the clinical data of 130 elderly patients with gallstones who underwent cholecystectomy in Nantong Hospital Affiliated to Nanjing University of Chinese Medicine from January 2022 to January 2023. Gastrointestinal quality of life index (GIQLI) was used to assess the QoL of all patients one month after surgery. Patients with GIQLI score < 121 points were included in the observation group (n=37), and those with GIQLI score ≥121 points were included in the control group (n=93). SPSS 20.0 was used for statistical analysis of the data. According to the data type, the t test orχ² test was used for comparison between groups. Multivariate logistic regression model was used to analyze the influencing factors of QoL one month after cholecystectomy. Results There were significant differences between the two groups in calculus characteristics, number of catheter insertions, gallbladder wall thickness, adhesion of the surrounding organs, Calot triangle adhesion, operative methods, and complications (χ²=10.569,10.013,4.134,4.767,5.121,8.353,8.190, P<0.05). Multivariate logistic regression analysis found silty calculi (OR=3.916, 95%CI 1.157-13.252), number of catheter insertions > 3 (OR=4.632,95%CI 1.143-18.773), gallbladder wall thickness > 5 mm (OR=4.125,95%CI 1.071-15.887), adhesion of surrounding organs (OR=3.854,95%CI 1.154-12.864), Calot triangle adhesion (OR=4.609,95%CI 1.237-17.170), and postoperative complications (OR=4.108,95%CI 1.214-13.903) were an independent risk factor for QoL in elderly patients with cholecystectomy (P<0.05). Conclusion Silty calculi, number of catheter insertions, gallbladder wall thickness, adhesion of the surrounding organs, Calot triangle adhesion, and postoperative complications are significantly associated with poor quality of life in patients after cholecystectomy. Preoperative comprehensive evaluation of these factors and targeted measures should be taken to improve their postoperative quality of life.