Objective: This was a prospective open study to establish the efficacy, tolerability, and problems associated with the use of topiramate as first-choice drug in children with infantile spasms. Methods: Open-label follow-up study, ranging from 24 to 36 months, of the cases of 54 patients with infantile spasms treated initially with topiramate as first-choice drug. Results: Thirty-one patients (57.4%) were seizure free for more than 24 months; 9 patients were treated with topiramate alone and 22 patients with topiramate plus nitrazepam and/or valproate. In 44 cases (81.4%), the reduction of seizure frequency from baseline was greater than 30%, whereas in 10 cases (18.6%), there was poor or no response. The average dosage applied was 5.2 mg/kg per day (maximum dosage, 26 mg/kg per day; minimum dosage, 1.56 mg/kg per day). Adverse events occurred in 14 patients (26%). They included poor appetite leading to anorexia, absence of sweating, and sleeplessness. Conclusions: Topiramate proves to be an effective and safe first-choice drug not only as adjunctive but also as monotherapy of infantile spasms in children younger than 2 years.