To evaluate the impact of inclusion of an anti-seizure medication (ASM) weaning protocol in a neonatal seizure pathway on the percent of infants discharged on ASMs. This cohort study included surviving infants with acute symptomatic seizures treated with ASMs across three institutions. We evaluated infants in 2 epochs, pre- and post-implementation of the ASM weaning protocol. The primary outcome was discharge on ASM. Of 116 included infants, the percent of infants discharged on ASMs was 69% in epoch 1 versus 34% in epoch 2 (p < 0.001). There was no significant difference between epochs in recurrence of seizures after discharge by 1 year of age (p = 0.125). There was an annual decrease in the percent of infants discharged on ASM across all institutions. Inclusion of a formal ASM weaning protocol as part of an institutional seizure pathway reduced percent of infants with acute symptomatic seizures discharged on ASM.