Conflicting data exist for the appropriate management of a neonate with supraventricular tachycardia (SVT). We sought to assess postnatal prescribing trends for neonates with SVT and to evaluate if there were therapy-specific mortality and resource utilization benefits. Nationally distributed data from 44 pediatric hospitals in the 2004 to 2015 Pediatric Health Information System database were used to identify patients admitted at 52 days of age with structurally normal hearts and treated with an antiarrhythmic medication. Outcome variables were mortality, cost, and length of stay (LOS). Multivariable models and propensity score matching were used. There were 2,657 neonates identified with a median gestational age of 37 weeks (interquartile range 34 to 39). Digoxin and propranolol were most commonly prescribed; digoxin use steadily decreased to 23% of antiarrhythmic medication administrations over the study period, whereas propranolol increased to 77%. Multivariable comparisons revealed that the odds of mortality for neonates on propranolol were 0.32 times those on digoxin (95% confidence interval 0.17 to 0.59; p <0.001); hospital costs were $16,549 lower for propranolol versus digoxin (95% confidence interval $5,502 to $27,596, p = 0.003). No difference was found for LOS. Propensity score matching and subset analyses of patients with only arrhythmia diagnostic codes confirmed mortality benefits for propranolol, although longer LOS was observed. In conclusion, propranolol use for the neonate with SVT is associated with lower in-hospital mortality and hospital costs compared with digoxin. (C) 2017 Elsevier Inc. All rights reserved.