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Objectives: The aim of this study was to investigate the clinical efficacy and safety of cefiderocol in the treatment of acute bacterial infections. Methods: The PubMed, Embase and Cochrane Library databases as well as the clinical trials registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched up to 8 November 2020. Only randomised controlled trials (RCTs) that compared the treatment efficacy of cefiderocol with that of other antibiotics for adult patients with acute bacterial infections were included in this meta-analysis. The primary outcome was clinical response at test of cure (TOC). Results: Three RCTs, including one phase 2 and two phase 3 trials, were included. No significant difference in clinical response rate was observed between cefiderocol and comparators [odds ratio (OR) = 1.04]. In a subgroup analysis, no significant difference was observed in the clinical response at TOC between cefiderocol and comparators in patients with nosocomial pneumonia (OR = 0.92) or complicated urinary tract infection (OR = 1.28). In addition, all-cause mortality at Days 14 and 28 did not differ between the cefiderocol and control groups (14-day mortality, OR = 1.25; 28-day mortality, OR = 1.12). Furthermore, cefiderocol was associated with similar microbiological response to comparators at the TOC assessment (OR = 1.44). Finally, cefiderocol was associated with a similar risk of adverse events as comparators. Conclusion: Cefiderocol can achieve similar clinical and microbiological responses as comparators for patients with serious bacterial infections. In addition, cefiderocol shares a safety profile similar to that of comparators.