OBJECTIVE: To employ the neonatal seizure framework developed by the International League Against Epilepsy (ILAE) Neonatal Task force to assess its usefulness in determining the etiology of neonatal seizures. METHODS: The members of the ILAE Neonatal Task Force evaluated 157 seizures from 146 neonates to determine internal validity and associations between semiology and a specific etiology. RESULTS: Provoked neonatal electrographic and electroclinical seizures were due to multiple etiologies. For electroclinical seizures, unilateral clonic seizures were typically seen with vascular etiologies, focal tonic seizures and sequential seizures with genetic etiologies, and myoclonic seizures with inborn errors of metabolism. Electrographic seizures were often seen in hypoxic-ischemic encephalopathy or vascular etiologies. SIGNIFICANCE: These data suggest that the ILAE neonatal seizure classification may be used as a bedside tool to aid and guide workup to determine the etiology of seizures.