Introduction: There is controversy regarding the optimal minimal mechanical ventilator support from which to extubate children. While some argue effort of breathing on minimum CPAP best estimates conditions after extubation, others suggest pressure support should be added to overcome perceived resistance from the endotracheal tube. Methods: We conducted a prospective observational trial in endotracheally intubated children in the pediatric and cardiac ICUs at Children’s Hospital Los Angeles. Using esophageal manometry we measured effort of breathing with pressure rate product (PRP = peak-to-trough change in esophageal pressure * respiratory rate) under 4 conditions: Pressure support 10/5 cmH20 (PS), CPAP 5 cmH20 (CPAP), and spontaneous breathing, 5 (5min) and 60 (60min) minutes after extubation. We used repeated measures ANOVA with Scheffe’s test for multiple comparisons to compare PRP, with a log transformation. We used the combination of calibrated Respiratory Inductance Plethysmography (RIP) flow and esophageal pressure to evaluate for inspiratory flow limitation from UAO after extubation. This was used for subgroup analysis to exclude UAO as a confounder. We also stratified by endotracheal tube size ≤ 4.0. Results: One-Hundred and seventy one children were included. Median (IQR) age was 5 (1, 18) months. Median (IQR) PRP for the 4 conditions were: PS 100 (50,200), CPAP 200 (120,325), 5min 300 (170,500), 60min 250 (140,420). PRP was significantly different under these 4 conditions using repeated measures ANOVA (p<0.001); multiple comparisons demonstrated PS was lower than the 3 other values and CPAP was lower than the 5 min value (p<0.001). When limiting to those without UAO (n=128), PRP on PS was significantly lower than the other 3 conditions (p<0.001) with no difference between CPAP and post extubation values (p>0.2): PS 100 (50,180), CPAP 200 (120,300), 5min 250 (150,375), 60min 200 (120,315). When limiting to those without UAO and endotracheal tubes ≤ 4.0 (n=95), PRP on PS was significantly lower than the other 3 conditions (p<0.001) with no difference between CPAP and post extubation values (p>0.2): PS 110 (60,200), CPAP 240 (140,300), 5min 300 (180,400), 60min 230 (130,350). Conclusions: Effort of breathing on CPAP most closely estimates post-extubation effort of breathing, and the addition of pressure support significantly underestimates post-extubation effort. This finding holds even for children with small endotracheal tubes, controlling for post-extubation UAO. Therefore, children should be extubated from CPAP, regardless of endotracheal tube size.