Objective To systematically evaluate the application efficacy of failure mode and effect analysis (FMEA) management mode in the prevention and control of healthcare-associated infection (HAI). Methods Li-terature on the application of FMEA management mode in HAI prevention and control were retrieved from PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM). Two researchers independently screened the literature, extracted data, and conducted cross checking. Risk and quality assessments were performed on the included studies of randomized controlled trials by ROB tool, the included cohort studies were scored by Newcastle-Ottawa (NOS) scale, and Meta-analysis was conducted by RevMan 5.4 software. Results A total of 22 studies involving 42 815 patients were included in the analysis, with 21 784 in the FMEA management mode group and 21 031 in the control group. Meta-analysis results showed that the incidence of HAI in the FMEA management mode group was lower than that in the control group (OR=0.31, 95%CI ［0.24, 0.40］). Compared with the conventional management mode, incidences of superficial surgical site infection (OR=0.53, 95%CI ［0.36, 0.78］), respiratory system infection (OR=0.44, 95%CI ［0.35, 0.56］), urinary system infection (OR=0.45, 95%CI ［0.38, 0.53］), and blood system infection (OR=0.29, 95%CI ［0.18, 0.45］) in the FMEA management mode group were all lower (all P<0.01). Conclusion The application of FMEA management mode in HAI prevention and control can reduce the incidence of HAI, which should be actively promoted in hospital management.