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Introduction: Respiratory arrest is the leading cause of pediatric cardiac arrest. Pediatric CRP guidelines therefore focus on respiratory support during CPR, but the optimal approach to oxygen delivery and coronary perfusion during pediatric CPR is not known. Animal studies reported that chest compressions superimposed with constant high distending pressure, or sustained inflation (CC+SI), significantly reduces time to return of spontaneous circulation (ROSC) compared to 3:1 chest compression:ventilation in neonatal piglets or chest compressions with asynchronous ventilation (CCaV) in pediatric piglets. During CC+SI, both cardiovascular and respiratory parameters were improved, which resulted in the faster time to ROSC. Hypothesis: In the current study, we hypothesized that CC+SI, compared to CCaV, would reduce time to ROSC in pediatric piglets with asphyxia-induced cardiac arrest. Methods: Twenty-eight pediatric piglets (21-24 days old, 7.5-9.2 kg) were anesthetized, intubated, instrumented, and exposed to 30 min normocapnic hypoxia followed by asphyxia. Piglets were then randomized to, and received, either CC+SI or CCaV for resuscitation (n=14 per group). Resuscitative efforts were continued until ROSC was achieved, or up to a maximum of 10 min. Hemodynamic parameters were monitored throughout the experiment and up to 30 min post-ROSC. Results and Conclusions: Overall, the mean (SD) time to ROSC was 208 (190) sec with CC+SI and 388 (258) sec with CCaV (p=0.045) (Table 1). There was a 100% increase in the number of piglets achieving ROSC with CC+SI compared to CCaV (CC+SI n=12 versus CCaV n=6, p=0.046). Median minute ventilation in the CC+SI group was 2,315 mL/min compared with 354 mL/min in the CCaV group (p=0.0001). Both systolic and diastolic blood pressure were higher in the CC+SI group, compared to the CCaV group throughout resuscitation. In summary, CC+SI improved time to ROSC and increased the number of piglets achieving ROSC. There was significantly higher minute ventilation with CC+SI, compared to CCaV, and both systolic and diastolic blood pressure were higher throughout resuscitation with CC+SI compared to CCaV. Studies in pediatric patients using CC+SI are warranted.