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Background: Emergency cholecystectomy is the mainstay in treating acute cholecystitis (AC). In actual practice, perioperative prophylactic antibiotics are used to prevent postoperative infectious complications (PIC), but their effectiveness lacks evidence. We aim to investigate the efficacy of prophylactic antibiotics in emergency cholecystectomy., Methods: We searched PubMed, Embase, Cochrane CENTRAL, Web of Science (WOS), and Scopus up to June 14, 2023. We included randomized controlled trials (RCTs) that involved patients diagnosed with mild to moderate AC according to Tokyo guidelines who were undergoing emergency cholecystectomy and were administered preoperative and/or postoperative antibiotics as an intervention group and compared to a placebo group. For dichotomous data, we applied the risk ratio (RR) and the 95% confidence interval (CI), while for continuous data, we used the mean difference (MD) and 95% CI., Results: We included seven RCTs encompassing a collective sample size of 1747 patients. Our analysis showed no significant differences regarding total PIC (RR = 0.84 with 95% CI (0.63, 1.12), P = 0.23), surgical site infection (RR = 0.79 with 95% CI (0.56, 1.12), P = 0.19), distant infections (RR = 1.01 with 95% CI (0.55, 1.88), P = 0.97), non-infectious complications (RR = 0.84 with 95% CI (0.64, 1.11), P = 0.22), mortality (RR = 0.34 with 95% CI (0.04, 3.23), P = 0.35), and readmission (RR = 0.69 with 95% CI (0.43, 1.11), P = 0.13)., Conclusion: Perioperative antibiotics in patients with mild to moderate acute cholecystitis did not show a significant reduction of postoperative infectious complications after emergency cholecystectomy. (PROSPERO registration number: CRD42023438755)., (© 2024. The Author(s).)