Abstract: Objective: To explore the predictive value of oxygenation index (OI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) within 28 days of death in pediatric intensive care unit (PICU) patients with acute respiratory failure (ARF) requiring invasive mechanical ventilation. Methods: Clinical data of 111 children with ARF who were admitted to PICU in the First Affiliated Hospital of Guangxi Medical University and required invasive mechanical ventilation from 2017 to 2019 were collected and analyzed, including the Pediatric Risk of Mortality Ⅲscores (PRISM Ⅲ), OI, NT-proBNP, and survival within 28 days after mechanical ventilation. Univariate and multivariable logistic regression analysis were used to assess the risk factors for death within 28 days in children with ARF. Receiver operating characteristic (ROC) curves were drawn to evaluate the effect of NTproBNP, OI, and age in predicting 28-day survival. Results: The median age was 12 months (4.5-66 months), with 79 survivors (71.17%) and 32 non-survivors (28.83%) within 28 days. OI was significantly higher, while NTproBNP was significantly lower in the non-survivor group compared with the survivor group (both P< 0.05), and there was no difference in the PRISM Ⅲbetween the two groups within 24 h (P> 0.05). Multivariate logistic regression analysis showed that age, OI and NT-proBNP were independent risk factors for death in children with ARF within 28 days (P< 0.05). The area under ROC curve (AUC) of age, OI, NT-proBNP and their combination were 0.6250, 0.6036, 0.6028 and 0.6572, respectively. The combination of age+OI+NT-proBNP had a better prediction effect. Conclusion: In children with ARF requiring mechanical ventilation, age, OI and NT-proBNP levels in the first 24 hours are associated with 28-day mortality risk. The combination of age, OI, and NT-proBNP is helpful for early identification of mortality risk in intubated children with ARF.