The objective of this study was to examine the factors associated with the occurrence of behavioral and cognitive abnormalities in children treated with topiramate. A retrospective chart review of patients up to 18 years of age who had been treated with topiramate at a tertiary epilepsy center was performed. Behavioral or cognitive abnormalities were observed in 11 (14.6%) of 75 children between 2 weeks and 4 months after initiation of therapy. The mean dosage (4.6 mg/kg daily) at which these abnormalities were observed was similar to the mean final dose (5.8 mg/kg daily) in children without abnormalities. The mean rate of dosage increase was 0.72 mg/kg weekly and 0.7 mg/kg weekly in those with and without abnormalities, respectively. Five of the 11 children with behavioral or cognitive abnormalities had a previous history of behavioral or cognitive abnormalities, but only nine of the 64 children without abnormalities had a previous history of behavioral or cognitive abnormalities (P = 0.03). Lamotrigine was used concurrently in four of the 11 children with behavioral or cognitive abnormalities but in only seven of the 64 children without abnormalities (P = 0.05). Behavioral and cognitive abnormalities in children treated with topiramate do not appear to be related to the rate of dosage increase. A previous history of behavioral problems and the concurrent use of lamotrigine may be predisposing factors.