We evaluated the safety and efficacy of ethyl loflazepate in children with epilepsy. The study group comprised 21 outpatients (4 by generalized, 17 by localization-related) aged between 9 months and 17 years. Ethyl loflazepate was administered at a dose of 0.015 mg/kg/day twice daily. The final mean dose was 1.35 mg/day. The mean number of prior antiepileptic drugs was 5.7. The entire treatment period was more than 24 months after ethyl loflazepate administration. Six children (28.6%) became seizure-free for the entire study 6 months after administration, 11 (52.4%) had a seizure reduction of more than 50% for over entire 24 months. The mean number of co-medications was 2.4. Adverse events occurred in only 1 patient. Responders, defined as reduction of ≥50% in seizure frequency, included 2/2 of patients with West syndrome and 15/17 (88.2%) with localization-related epilepsy. Ethyl loflazepate represents an important addition to the treatments available for refractory epilepsies in children.