Neonatal seizures are one of the most common neurological disorders in infants. However, the optimal treatment strategy for neonatal seizures remains controversial and there is little data regarding current treatment of neonatal seizures. In this study we describe the current treatment of neonatal seizures and variation in practice among 31 pediatric hospitals in the United States. We retrospectively identified 6099 infants hospitalized in the first month of life in one of 31 pediatric hospitals participating in the Pediatric Health Information System, with a discharge diagnosis of seizure. As expected, most treated infants received phenobarbital. However, there was significant interhospital variability for all treatments studied including any antiepileptic drug treatment, phenytoin treatment, antiepileptic drug treatment through discharge, number of antiepileptic drugs used, and treatment with pyridoxine (P < .001). These findings highlight the need for rigorous controlled outcome studies to determine optimal therapy for neonatal seizures and devise treatment standards.