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Summary: Purpose: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain. Methods: We directly compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in 35 healthy subjects by using a double-blind, randomized crossover design with two 5-week treatment periods. During each treatment condition, subjects received either GBP, 2,400 mg/day, or CBZ (mean, 731 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean, 8.3 μg/ml). Subjects were tested at the end of each AED treatment period and in four drug-free conditions [two pretreatment baselines and two posttreatment washout periods (1 month after each AED)]. The neuropsychological test battery included 17 measures yielding 31 total variables. Results: Direct comparison of the two AEDs revealed significantly better performance on eight variables for GBP, but none for CBZ. Comparison of CBZ and GBP to the nondrug average revealed significant statistical differences for 15 (48%) of 31 the variables. Pairwise follow-up analyses of the 15 variables revealed significantly better performance for nondrug average on 13 variables compared with CBZ, and on four compared with GBP. GBP was better than nondrug average on one variable. Conclusions: Although both CBZ and GBP produced some effects, GBP produced significantly fewer untoward cognitive effects compared with CBZ at the dosages used in this study.