Abstract INTRODUCTION Acute calculous cholecystitis (ACC) is the second surgical cause of emergency consultation in the Western world. According to the Tokyo International Guidelines 2018 (TIG18), the treatment of choice is laparoscopic cholecystectomy in patients with mild or moderate cholecystitis. However, in severe cases there is a great variability of therapeutic options. We analyzed the adequacy of antibiotic therapy by studying intraoperative cultures (bile and peritoneal fluid) and preoperative blood cultures, to identify the effect of this antibiotic therapy on complication and mortality rates. MATERIAL AND METHODS A retrospective unicentric study on a prospective database of 725 ACCs between 2012 and 2016. More than 200 general, clinical, postoperative and microbiological variables are collected, including the antibiogram of the isolated germs in order to determine the adequacy of each administered antibiotic. RESULTS Cultures were performed in 76.1% of the cases, with a greater tendency to cultivate in older patients, men or with greater severity according to TIG18 (p < 0.001). Cultured patients had a higher rate of postoperative complications (p = 0.001). Patients who received adequate empirical antibiotic therapy had a lower rate of complications (50% vs 64%;p=0.037) and lower mortality (2.8% vs 11.8%;p=0.003) compared to patients with resistant germs to the antibiotic therapy given, especially important in severe ACC (3.7% vs 15.7%;p=0.022). CONCLUSIONS Adequate empirical antibiotic therapy is associated with fewer complications, as well as a lower mortality rate, especially in severe ACCs. Patients with severe ACC will probably require empirical broad-spectrum antibiotic coverage.