Objective To evaluate the effect of healthcare failure mode and effect analysis (HFMEA) combined with enhanced link quality management as a strategy on the prevention and control of ventilator-associated pneumonia (VAP) in the respiratory intensive care unit (RICU), and provide evidence for optimizing clinical infection control processes. Methods A retrospective study was conducted. Invasively mechanically ventilated RICU patients who received routine prevention and control of VAP in Wuhan Pulmonary Hospital from January to December 2023 were selected as the control group. Patients who underwent HFMEA combined with enhanced link quality management for VAP prevention and control in RICU of the same hospital from January to December 2024 were selected as the trial group. Differences in quality score of VAP prevention and control key links, compliance rate of prevention and control measures, VAP incidence, and satisfaction of healthcare workers (HCWs) under different management modes between the two groups of patients were compared. Results The control group consisted of 129 patients who received mechanical ventilation for 1 526 days, and the trial group consisted of 161 patients who received mechanical ventilation for 1 409 days. The total score for the quality assessment of key links in VAP prevention and control was (60.15±5.52) points for the control group and (90.00±4.05) points for the trial group. The total score and quality score of each link quality in the trial group were all higher than those in the control group, and differences were all statistically significant (all P<0.05). The compliance rate of VAP prevention and control core measures was 62.64% in the control group and 85.09% in the trial group. The overall compliance rate and compliance rate of various measures in the trial group were all higher than those in the control group, and differences were all statistically significant (all P<0.05). The average mechanical ventilation time of patients in the trial group was (8.75±4.20) days, which was shorter than (11.83±5.80) days of the control group, with statistically significant difference (P<0.001). The incidences of VAP in trial group and control group were 9.23‰ and 19.00‰, respectively, difference was statistically significant (P=0.026). The job satisfaction rate of HCWs in the trial group was 93.94%, while that in the control group was 72.73%, with statistically significant difference (P=0.007). Meanwhile, the trial group had a higher percentage of "very satisfied" (27.27% vs 15.15%) and a lower percentage of "dissatisfied" (6.06% vs 27.27%). Conclusion The joint strategy of HFMEA combined with enhanced link quality management can help to improve the implementation efficiency of VAP prevention and control measures, reduce the incidence of VAP, and enhance the satisfaction of HCWs towards VAP prevention and control.