BACKGROUND Recent evidence from juvenile animal models has shown that exposure to anesthetic drugs above threshold doses during a critical neurodevelopmental window causes widespread neuronal apoptosis, resulting in irreversible brain damage and subsequent learning difficulties. The relevance of this to human infants having general anesthesia for minor surgery is unknown. In this pilot observational cohort study, we sought to determine whether children exposed to general anesthesia for minor surgery during infancy exhibited differences in academic achievement at age 12 years, as evidenced by (1) lower aggregate scores in the Singapore standardized Primary School Leaving Examination (PSLE) and (2) formally diagnosed learning disability, compared with children who were never exposed to anesthesia or sedation. METHODS We compared 100 full-term, apparently healthy children aged 12 years who were exposed to general anesthesia for minor surgery before age 1 at our institution with an age-matched cohort of 106 children who were never exposed to anesthesia or sedation. Parents of children completed a 20-minute telephone interview with questions regarding their children's medical history, school environment, and home environment. RESULTS The difference in mean PSLE aggregate scores (3.0; 95% confidence interval [CI], -8.3 to 14.3) between exposed (197.0; 95% CI, 185.6-208.4) and control groups (194.0; 95% CI, 182.9-205.1) was not statistically significant (P = 0.603). The presence of formally diagnosed learning disability was 15% (15 of 100) in the exposed group compared with 3.77% (4 of 106) in the control group (P < 0.001). The odds ratio for a formal diagnosis of learning disability in those exposed to general anesthesia relative to controls was 4.5 (95% CI, 1.44-14.1). CONCLUSION The odds of a formal diagnosis of learning disability by age 12 years in apparently healthy children exposed to general anesthesia for minor surgery during infancy were 4.5 times greater than their peers who had never been exposed to anesthesia. However, study precision was inadequate to detect a clinically relevant difference in PSLE scores.