SUMMARY OBJECTIVE Acute calculous cholecystitis (AC) is a frequently encountered emergency surgery disease and its standard treatment is cholecystectomy. In patients with high risk in surgery, antibiotic treatment (AT) is important. In routine clinical practices, antibiotics are frequently used either as single or in combination in the treatment of AC. This study examined whether or not combined antibiotic treatment (CAT) had superiority over single antibiotic treatment (SAT) in AC. METHODS Patients with cholecystitis who received treatment in the period of 2016-2019 were retrospectively examined. The treatment procedures applied, patient findings, and laboratory data were analyzed using relevant statistical software. The patients were categorized into groups based on the treatment approaches applied, and the effects of SAT and CAT on infection parameters were analyzed. RESULTS In all, 184 patients received treatment for AC, with a mean age of 57.7, and the female-to-male ratio was 77:107. Of these, 139 patients received SAT and 45 received CAT. No significant difference was found in terms of effectiveness between the SAT and CAT in the patients who received early cholecystectomy treatment and those who received medical treatment with noninvasive intervention. CONCLUSIONS In patients with AC, antibiotics are commonly used either as single or in combination for prophylaxis and therapeutic purposes. As no significant difference was observed between single and combined use in terms of treatment effectiveness and hospitalization duration, CAT is not recommended due to its possibility of allergic side effects, toxicity, and cost-increasing effects.