Background In the present study, we aimed to compare the efficacy and safety of plazomicin with comparators for the treatment of Enterobacterales infections. Methods Randomized controlled trials (RCTs) assessing plazomicin for Enterobacterales infections were searched on the PubMed, Embase, and Cochrane Library databases. Meta-analyses were used to evaluate the efficacy and safety in RCTs. Results A total of 3 RCTs consisting of 761 patients were included in the present analysis. The study population included complex urinary tract infections (cUTIs), bloodstream infections (BSIs), and hospital-acquired pneumonia (HAP). Plazomicin had a clinical remission rate in the modified intention-to-treat (MITT) population that was similar to that of comparators (odds ratio [OR], 1.02; 95% CI, 0.60-1.73; I-2 = 45%) in the pooled analysis of the 3 studies. The overall microbiologic eradication rate in the microbiological MITT (mMITT) population was similar to that of the comparators group (OR, 1.46; 95% CI, 0.72-2.95; I-2 = 0%). However, the microbiologic recurrence rate of plazomicin for Enterobacterales was lower than that in the comparators group (OR, 0.38; 95% CI, 0.17-0.86; P = .02; I-2 = 0%). No signi?cant differences were found between plazomicin and comparators for the risk of any adverse events (OR, 0.78; 95% CI, 0.55-1.11; I-2 = 0%). Conclusions Plazomicin is as good as comparators in terms of efficacy and tolerance in the treatment of Enterobacterales infections. Therefore, plazomicin is a suitable choice for antibiotic treatment in adult patients with cUTIs, BSIs, or HAP.