OBJECTIVES: The purpose of this work was to compare the efficacy of propofol, a hypnotic agent, to the regimen of morphine, atropine, and suxamethonium as an induction agent for nonemergency neonatal endotracheal intubation. We hypothesized that propofol aids intubation by allowing the continuation of spontaneous breathing. PATIENTS AND METHODS: We conducted a randomized, open-label, controlled trial of infants who required nonemergency endotracheal intubation. Primary outcome was successful intubation confirmed by chest auscultation and clinical examination of the infant. RESULTS: Infants randomly assigned to propofol (n = 33) and the morphine, atropine, and suxamethonium regimen (n = 30) were comparable in median gestational age (27 vs 28 weeks), birth weight (1020 vs 1095 g), weight at intubation (1068 vs 1275 g), and age at intubation (4 vs 3 days). Sleep or muscle relaxation were achieved within 60 seconds in both groups, but time to achieve successful intubation was more than twice as fast with propofol (120 vs 260 seconds). Blood pressure and heart rates were not different, but intraprocedural oxygen saturations were significantly lower in infants on the morphine, atropine, and suxamethonium regimen (trough arterial oxygen saturation: 60% vs 80%). Nasal/oral trauma was less common, and recovery time was shorter (780 vs 1425 seconds) in the propofol group. No significant adverse effects were seen in either group. CONCLUSIONS: Propofol is more effective than the morphine, atropine, and suxamethonium regimen as an induction agent to facilitate neonatal nasal endotracheal intubation. Importantly, hypoxemia was less severe, probably because of the maintenance of spontaneous breathing. A controlled environment may have promoted the ease of intubation, resulting in less trauma. The shorter duration of action would be advantageous in a compromised infant.