Background: Acetaminophen is the most commonly recommended over-the-counter drug during pregnancy yet is an endocrine-disrupting medication. This study’s objective was to evaluate the neurological effects of prenatal acetaminophen exposure, up to 48 months of age.Methods: In this prospective cohort study, 586 women in the UCSD MothertoBaby Study were surveyed throughout pregnancy and 600 children were followed between 12 and 48 months of age. Exposure was operationalized based on categorical exposure to acetaminophen (none, low, moderate, high). Four neurological scales (ASQ, MCHAT, WG, WS) were used to evaluate neurodevelopment. Results: ASQ gross motor scores for the low exposure group were significantly lower than those unexposed (β = -2.036, p = 0.0053, 95% CI(-5.30, -0.929)). Adjusted ASQ problem solving scores by quantile showed individuals in both the low (β = -2.471, p = 0.0402, 95% CI(-4.98,-0.113)) and high (β = -2.958, p = 0.0158, 95% CI(-5.67,-0.590)) groups had significantly lower scores than those unexposed. On the WS test, varying levels of acetaminophen exposure was associated with a higher risk of failure to use absent object production (moderate exposure RR = 1.103, 95% CI (1.03, 1.18)), possessive tense (low exposure RR = 1.24, 95% CI (1.02, 1.49)), and combine words proficiently (high exposure RR = 1.13, 95% CI (1.02, 1.26)), compared to those unexposed. Conclusion: Prenatal acetaminophen exposure was a risk factor for lower ASQ and Words & Sentences scores. Results did not show an association between acetaminophen and neurological outcomes on all scales, indicating the need for additional research.