Background: In intensive care units (ICUs), the morbidity and mortality of ventilator-associated pneumonia (VAP) are relatively high, and this condition also increases medical expenses for mechanically ventilated patients, which will seriously affect the prognoses of critically ill patients. The purpose of this study was to determine the impact of bronchoscopy on the prognosis of patients with VAP undergoing invasive mechanical ventilation (IMV). Methods: This was a retrospective study based on patients with VAP from the Medical Information Mart for Intensive Care IV database. The outcomes were ICU and in-hospital mortality. Patients were divided based on whether or not they had undergone bronchoscopy during IMV. Kaplan-Meier (KM) survival curves and Cox proportional-hazards regression models were used to analyze the association between groups and outcomes. Propensity score matching (PSM) and propensity score based inverse probability of treatment weighting (IPTW) were used to further verify the stability of the results. The effect of bronchoscopy on prognosis was further analyzed by causal mediation analysis (CMA). Results: This study enrolled 1,560 patients with VAP: 1,355 in the no-bronchoscopy group and 205 in the bronchoscopy group. The KM survival curve indicated a significant difference in survival probability between the two groups. The survival probabilities in both the ICU and hospital were significantly higher in the bronchoscopy group than in the no bronchoscopy group. After adjusting all covariates as confounding factors in the Cox model, the HRs (95% CI) for ICU and in-hospital mortality in the bronchoscopy group were 0.33 (0.20-0.55) and 0.40 (0.26-0.60), respectively, indicating that the risks of ICU and in-hospital mortality were 0.67 and 0.60 lower than in the no-bronchoscopy group. The same trend was obtained after using PSM and IPTW. CMA showed that delta-red blood cell distribution width (RDW) mediated 8 and 7% of the beneficial effects of bronchoscopy in ICU mortality and in-hospital mortality. Conclusion: Bronchoscopy during IMV was associated with reducing the risk of ICU and in-hospital mortality in patients with VAP in ICUs, and this beneficial effect was partially mediated by changes in RDW levels.Copyright © 2022 Zhang, Li, Yuan, Lu, Li, Liu, Huang, Lyu and Yin.