ObjectivesTo assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures.DesignRetrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia.Setting22 US centres.PatientsInfants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM.ExposuresASM continued or discontinued at discharge.OutcomesDeath or moderate-to-severe disability at 18–22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre.ResultsOf 302 infants included, 61% were continued on ASMs at discharge (range 13%–100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05).ConclusionsIn infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18–22 months of age.