Introduction: Digoxin or propranolol are used as first-line enteral agents for treatment of infant supraventricular tachycardia. We used a large national database to determine whether enteral digoxin or propranolol was more effciacious as first-line infant supraventricular tachycardia therapy. Materials and Methods: The Pediatric Health Information System database was queried over 10 years for infants with supraventricular tachycardia initiated on enteral digoxin or propranolol monotherapy. Patients were excluded for Wolff–Parkinson–White, intravenous antiarrhythmics (other than adenosine), or death. Success was considered as discharge on the initiated monotherapy. Risk factors for successful monotherapy and risk factors for readmission for supraventricular tachycardia for patients discharged on monotherapy were determined. Results: A total of 374 patients (59.6% male) met the study criteria. Median length of stay was 7 days (interquartile range of 3–16 days). Patients had CHD (n=199, 53.2%) and underwent cardiac surgery (n=123, 32.9%), ICU admission (n=238, 63.6%), mechanical ventilation (n=146, 39.0%), and extracorporeal membrane oxygenation (n=3, 0.8%). Pharmacotherapy initiation was at median 37 days of life (interquartile range of 12–127 days) and 47.3% were initiated on digoxin. Success was similar between digoxin (73.1%) and propranolol (73.5%). Initial therapy with digoxin was not associated with success (odds ratio 1.01, 95% CI 0.64–1.61, p=0.93). Multivariable analysis demonstrated hospital length of stay (odds ratio 0.98, 95% CI 0.98–1.00) and involvement of a paediatric cardiologist (odds ratio 0.46, 95% CI 0.29–0.75) associated with monotherapy failure, and male gender (odds ratio 1.66, 95% CI 1.03–2.67) associated with monotherapy success. No variables were significant for readmission on multivariable analysis. Discussion: Digoxin or propranolol may be equally efficacious for inpatient treatment of infant supraventricular tachycardia.