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BACKGROUND: Studies relating diaphragm thickening fraction (DTF), delta esophageal pressure (ΔPes), and weaning outcomes are lacking in critically ill children. RESEARCH QUESTION: How well does DTF correlate with ΔPes and predict weaning and extubation outcomes? STUDY DESIGN AND METHODS: In this secondary analysis of children with ARDS from a single-center randomized control trial, DTF and ΔPes were measured daily during mechanical ventilation and during spontaneous breathing trials (SBTs; CPAP, 5 cm H2O). SBT outcomes were classified as early failure (SBT failure within 30 minutes), late failure (SBT failure between 30 and 120 minutes), and SBT success. Extubation outcomes were classified as prolonged noninvasive ventilation (NIV; > 72 hours), reintubation within 48 hours, and successful extubation. RESULTS: The study included 194 patients with 704 daily measurements. The correlation between the daily DTF and ΔPes was r = 0.10 (95% CI, 0.01-0.19). One hundred seventy-one SBTs showed successful results, 60 SBTs showed early failures, and 88 SBTs showed late failures, with no difference in the median SBT DTF among groups (early failure, 20% [95% CI, 10%-32%]; late failure, 18% [95% CI, 12%-26%]; and success, 19% [95% CI, 11%-28%]; P = .69). The SBT DTF was not predictive of extubation success or failure (reintubation or prolonged NIV; area under the receiver operating characteristic curve, 0.54 [95% CI, 0.44-0.64]), with the median SBT DTF of 19% (interquartile range [IQR], 11%-31%; n = 124) for those successfully extubated; 23% (IQR, 16%-30%; n = 12) for those reintubated; and 17% (IQR, 10%-23%; n = 30) for those who received prolonged NIV (P = .3). INTERPRETATION: Our research shows that DTF should be used with caution in children because it does not seem to have a strong correlation with measures of respiratory effort and does not reliably predict SBT or extubation outcomes.