BACKGROUND:: Although studies in neonatal animals show that anesthetics have neurotoxic effects, relevant human evidence is limited. We examined whether children who had surgery during infancy showed deficits in academic achievement. METHODS:: We attempted to contact parents of 577 children who, during infancy, had one of three operations typically performed in otherwise healthy children. We compared scores on academic achievement tests with population norms. RESULTS:: Composite scores were available for 287 patients. The mean normal curve equivalent score was 43.0 ± 22.4 (mean ± SD), lower than the expected normative value of 50, P < 0.0001 by one-sample Student t test; and 35 (12%) had scores below the 5th percentile, more than expected, P < 0.00001 by binomial test. Of 133 patients who consented to participate so that their scores could be examined in relation to their medical records, the mean score was 45.9 ± 22.9, P = 0.0411; and 15 (11%) scored below the 5th percentile, P = 0.0039. Of 58 patients whose medical records showed no central nervous system problems/potential risk factors during infancy, 8 (14%) scored below the 5th percentile, P = 0.008; however, the mean score, 47.6 ± 23.4, was not significantly lower than expected, P = 0.441. Duration of anesthesia and surgery correlated negatively with scores (r = -0.34, N = 58, P = 0.0101). CONCLUSIONS:: Although the findings are consistent with possible adverse effects of anesthesia and surgery during infancy on subsequent academic achievement, other explanations are possible and further investigations are needed.