Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.