Introduction: Neonatal seizures are associated with worsened neurodevelopmental outcomes. Phenobarbital, the only US Food and Drug Administration (FDA)–approved treatment for neonatal seizures, can cause neuronal apoptosis and may worsen neurodevelopmental outcomes. Lacosamide may be an efficacious treatment for neonatal seizures. Methods: We assessed the impact of lacosamide boluses on seizure burden in a retrospective cohort of 15 neonates monitored with video electroencephalography (EEG). Medication bolus times and seizure start/end times on EEG tracings determined change in seizure burden. Results: Seven patients received lacosamide as first- or second-line treatment and 8 as third-line or later. Average 4-hour seizure burden decreased from 13% to 3% following lacosamide boluses (P = .002). Reduction in seizure burden greater than 30% followed 79% of boluses. Lacosamide was well tolerated; one patient experienced mild asymptomatic episodic bradycardia that medication taper resolved. Conclusions: Lacosamide significantly decreased seizure burden in this cohort. Prospective studies of lacosamide treatment for neonatal seizures are warranted.