Background: Most common anesthetic agents have been implicated in causing neurodegeneration in the developing animal brain, leading to warnings regarding their use in children. We hypothesized that exposure to general anesthesia and surgery before 4y would associate with adverse neurodevelopmental outcomes at age 7-16y. Methods: This cohort study comprised 13,433 children enrolled in the Avon Longitudinal Study of Parents and Children – a prospective, population-based birth cohort born in 1991-1993 in South-West England. Children were grouped by none, single or multiple exposures to general anesthesia and surgery by 4y. Motor, cognitive, linguistic, educational, social and behavioral developmental outcomes were evaluated at 7-16y using school examination results, validated parent/teacher questionnaires or clinic assessments. Continuous outcomes were z-scored. P-value thresholds were corrected using false discovery rate procedures.Results: 46 neurodevelopmental outcomes were compared in 13,433 children: 8.3% (1,110)exposed singly and 1.6% (212) exposed multiply to general anesthesia and surgery. Of these,the following reached predefined levels of statistical significance (corrected P<0.00652):dynamic balance scores were 0.3SD (95% CI:0.1,0.5; p<0.001) lower in multiply exposed children; manual dexterity performance was 0.1SD (95% CI:0.0,0.2, p=0.006) lower in singly and 0.3SD (95% CI:0.1,0.4, p<0.001) lower in multiply exposed children; and social communication scores were 0.1SD (95% CI:0.0,0.2; p=0.001) and 0.4SD (95% CI:0.3,0.5;p<0.001) lower in singly and multiply exposed children, respectively. General anesthesia and surgery were not associated with impairments in the remaining neurodevelopmental measures including: general cognitive ability; attention; working memory; reading, spelling, verbal comprehension and expression; behavioral difficulties; or national English,mathematics and science assessments (all ≤0.1SD; corrected P>0.00652).Conclusions: Early childhood general anesthesia and surgery were not associated with a global picture of clinically and statistically significant neurodegenerative effects, providing reassurance about the neurotoxic potential of general anesthesia. Exposure to anesthesia and surgery was associated with significantly lower motor and social linguistic performance.