Objectives: To determine the frequency and severity of clinically significant events of spitting up in normal newborns during the first 24 hours of life and to correlate the events with sleeping position.Design: Prospective observational study. Participants: Healthy full-term newborns (n = 3240) (Ն37 weeks estimated gestational age) during the first 24 hours of life.Outcome Measures: Frequency of, and intervention required for, spitting up in supine, side-lying, and prone positions while asleep and awake.Results: Of the 3240 infants, 96.6% did not spit up during sleep. A total of 142 episodes of spitting up were documented in 111 newborns during sleep. While the newborns were supine and asleep, there were 130 episodes of spitting up. Of these episodes, 55% did not require any intervention, 37% only required brief suctioning with a bulb syringe, 6% required gentle stimulation, and 2% required wall suction. Both nurseries had a policy that newborns should sleep supine; therefore, only 6 newborns were noted to have spitting up episodes while lying on the side, with 66.7% requiring no intervention and 33.3% requiring bulb syringe. No episodes of apnea, cyanosis, documented aspirations, neonatal intensive care unit admissions, or deaths from spitting up were noted. Conclusions:We conclude that clinically significant spitting up occurs infrequently in hospital newborn nurseries while the newborns are asleep. Fewer than 4% of newborns spit up while sleeping in the supine position in the first 24 hours of life, and none required significant intervention or experienced serious sequelae.