Neuropsychologic data are presented from a randomized, double-blind, placebo-controlled, multicenter study with placebo, topiramate 50 mg/day, and topiramate 100 mg/day. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and cognitive adverse events were used to evaluate neurocognitive effects of topiramate. Topiramate 100 mg/day vs placebo was associated with slight statistically significant score increases, indicating slowing, from baseline vs placebo in three CANTAB measures: five-choice reaction time (P = 0.028), pattern recognition memory mean correct latency (P = 0.027), and rapid visual information processing mean latency (P = 0.040). No other patterns related to topiramate treatment were observed in measurements of learning, memory, and visual information processing, except for potential improvement with topiramate 100 mg/day vs placebo in spatial span total errors (accuracy test) (P = 0.040). The most common cognitive and neuropsychiatric adverse events with a higher incidence in the topiramate 50 and 100 mg/day groups vs placebo were anorexia (9% and 11% vs 3%), insomnia (9% and 3% vs 3%), fatigue (6% and 9% vs 6%), and dizziness (6% and 9% vs 0%). Thus, topiramate 100 mg/day was associated with modest increases in psychomotor reaction times. Learning, memory, and executive function were unchanged. The tolerability profile, including cognitive adverse events, appeared to be acceptable.