BACKGROUND Antiseizure medications (ASMs) are the primary treatment for epilepsy; however, some prospective cohort studies in adults suggested that the efficacy of the third and subsequent ASM treatments are poor. Thus, we aimed to assess the outcomes of ASM treatment in new-onset pediatric epilepsy. METHODS We retrospectively studied 281 pediatric patients diagnosed with epilepsy, in which the first ASM was prescribed between July, 2015, and June, 2020, at Hiroshima City Funairi Citizens Hospital. We reviewed their clinical profiles and seizure outcomes at the end of the study in August, 2022. Seizure freedom was defined as having no seizures for the previous 12 months or longer. RESULTS Age at the onset of epilepsy ranged from 22 days to 186 months (mean: 84 months). The most frequent classifications of the types and syndromes of epilepsy were focal epilepsy (n = 151, 53.7%), followed by generalized epilepsy (n = 30, 10.7%), and self-limited epilepsy with centrotemporal spikes (n = 20, 7.1%). During the first ASM regimen, 183 out of the 281 (65.1%) patients became seizure free. During the second ASM regimen, 47 out of the 92 (51.1%) patients became seizure free. Only 15 out of the 40 (37.5%) patients who tried the third and subsequent ASM regimen became seizure free, while none became seizure free after the sixth and subsequent ASM regimen. CONCLUSIONS The efficacy of ASM treatment after the third and subsequent regimen was poor in children, as well as in adults. It is important to reconsider whether there are indications for treatments other than ASM.