LAUSR

&NA; Rationale: The ARDS Network (ARDSNet) used a positive end‐expiratory pressure (PEEP)/FiO2 model in many studies. In general, pediatric intensivists use less PEEP and higher FiO2 than this model. Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/FiO2 model had higher mortality. Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/FiO2 protocol. Four distinct datasets were combined for analysis. We extracted time‐matched PEEP/FiO2 values, calculating the difference between PEEP level and the ARDSNet‐recommended PEEP level for a given FiO2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP. Measurements and Main Results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of FiO2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32‐3.17). Findings were similar after propensity‐based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24‐3.22). Conclusions: Patients with PARDS managed with lower PEEP relative to FiO2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.