Background: Recently, sustained inflations (SI) during chest compression (CC) (CC+SI) have been suggested as an alternative to the current approach during neonatal resuscitation. No previous study compared CC+SI using CC rates of 90/min to the current 3:1 compression:ventilation ratio (C:V). Objective: To determine whether CC+SI versus a 3:1 C:V reduces the time to the return of spontaneous circulation (ROSC) and improves hemodynamic recovery in newborn piglets with asphyxia-induced bradycardia. Intervention and Measurements: Term newborn piglets were anesthetized, intubated, instrumented, and exposed to 45-min normocapnic hypoxia followed by asphyxia. Cardiopulmonary resuscitation (CPR) was initiated when the heart rate decreased to 25% of baseline. Piglets were randomized into 3 groups: CC during SI at a rate of 90 CC/min (SI+CC 90, n = 8), a 3:1 C:V using 90 CC and 30 inflations (3:1, n = 8), or a sham group (n = 6). Cardiac function, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Results: CC+SI significantly reduced the median (IQR) time of ROSC, i.e., 34 s (28-156 s) versus 210 s (72-300 s) in the 3:1 group (p = 0.048). CC+SI also significantly reduced the requirement for 100% oxygen, improved respiratory parameters, and resulted in a similar hemodynamic recovery. Conclusions: CC+SI during CPR significantly improved ROSC in a porcine model of neonatal resuscitation. This is of considerable clinical relevance because improved respiratory and hemodynamic parameters potentially minimize morbidity and mortality in newborn infants.