Objective To analyze the clinical characteristics associated with hospital infections in patients with common bile duct stones treated by endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic common bile duct exploration (LCBDE), thereby providing a basis for selecting treatment strategies and formulating hospital infection prevention measures for such patients. Methods Patients with common bile duct stones at Jiangsu Provincial People’s Hospital between January 2020 and July 2023 were retrospectively selected and divided into ERCP and LCBDE groups according to their surgical methods. Basic patient data, length of hospital stay, hospitalization costs, perioperative infection-related indicators, and occurance of hospital infections were compared between groups. Results A total of 402 patients were enrolled, with 242 in the ERCP group and 160 in the LCBDE group. Significant differences were noted in smoking, alcohol consumption, history of lung diseases, history of heart diseases, history of cholecystectomy/biliary surgery, presence of cholecystitis, presence of cholecystolithiasis, number of stones, maximum stone diameter, common bile duct diameter, total hospital stay, and total expenses (P<0.05). Twenty-four hours before surgery, except for the neutrophil count, which was slightly higher in the ERCP group than that in the LCBDE group (P=0.043), the infection-related indicators did not differ significantly between the two groups (P>0.05). Twenty-four hours after surgery, the levels of serum white blood cell, neutrophil, and aspartate aminotransferase in the ERCP group were lower than those in the LCBDE group (P<0.05), and the levels of alkaline phosphatase and gamma-glutamyl transferase in the ERCP group were higher than those in the LCBDE group (P<0.05). A total of 179 bile samples were collected and tested, identifying 137 strains of pathogenic bacteria (78 in the ERCP group and 59 in the LCBDE group). In the ERCP group, 42 strains (53.85%) were Gram-negative bacteria, 34 strains (45.59%) were Gram-positive bacteria, and 2 strains (2.56%) were fungi; in the LCBDE group, 33 strains (55.93%) were Gram-negative bacteria and 26 strains (44.07%) were Gram-positive bacteria. No significant difference was observed in the composition of pathogenic bacteria between the two groups (χ2=1.174, P=0.695). Among the 402 patients, 38 cases of hospital infection occurred postoperatively, with an infection rate of 9.45%. The difference in the infection rate between the ERCP group and the LCBDE group were statistically significant (11.98% vs. 5.63%; χ2=4.550, P=0.033). The main sites of infection were bloodstream, lungs, and abdominal-pelvic cavity. Conclusions The predominant pathogens isolated after both ERCP and LCBDE are Gram-negative bacteria. Compared with LCBDE, ERCP has less impact on inflammatory markers, hospital stay, and costs, but has a higher incidence of hospital infections.