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To investigate the utility of continuous quantitative end-tidal CO2 (Etco2) monitoring for managing assisted ventilation in the delivery room (DR).This is a prospective randomized controlled trial. Infants who received positive pressure ventilation (PPV) were randomized to a control versus a monitored arm. In the monitored arm, the resuscitating team adjusted PPV based on Etco2 values. In the control arm, the team provided PPV based on clinical assessment. Etco2 levels after resuscitation and admission Pco2 levels were compared between groups.Fifty infants were enrolled, and 48 subjects had primary outcome data. Of those, 7 infants were intubated in the DR, 41 infants received PPV via mask until respiratory support could be maintained on continuous positive airway pressure alone. The median Etco2 levels at the end of resuscitation were 44 mm Hg (16-66 mm Hg) in the control arm and 43 mm Hg (29-59 mm Hg) in the monitored arm. The proportion of Etco2 levels outside of the prespecified range was 52.6% (control) and 33.3% (monitored) (P = .236). The median admission Pco2 levels were 57 mm Hg (36-110 mm Hg) in the control arm and 55 mm Hg (40-93 mm Hg) in the monitored arm. The proportion of admission Pco2 levels outside of the prespecified range was 33.3% (control) versus 37.5% (monitored) (P = .763).Etco2 monitoring in the DR did not reduce the proportion of admission Pco2 levels outside of the prespecified range in a population of infants supported mostly with noninvasive ventilation.