Early life exposures have been associated with pediatric eosinophilic esophagitis (EoE), but it is unknown if a similar association is present in adults. We aimed to assess the association between early life risk factors and development of EoE in adulthood. To do this, we conducted a case-control study which was nested within a prospective cohort study of adults undergoing outpatient endoscopy. Cases of EoE were diagnosed per consensus guidelines; controls did not meet these criteria. Subjects and their mothers were contacted to collect information on four key early life exposures: antibiotics taken during the first year of life, Cesarean delivery, preterm delivery (≤37 weeks’ gestation), and neonatal intensive care unit (NICU) admission. We calculated the odds of EoE given in each exposure and assessed agreement between subjects and their mothers. For the 40 cases and 40 controls enrolled, we observed a positive association between each of the early life exposures and development of EoE (antibiotics in infancy, OR = 4.64, 95% CI = 1.63-13.2; Cesarean delivery, OR = 3.08, 95% CI = 0.75-12.6; preterm delivery, OR = 2.92, 95% CI = 0.71-12.0; NICU admission, OR = 4.00, 95% CI = 1.01-15.9). Results were unchanged after adjusting for potential confounders, though only early antibiotic use had CIs that did not cross 1.0. Moderate to strong agreement was observed between 54 subject-mother pairs (antibiotics, K = 0.44, P = 0.02; Cesarean delivery, K = 1.0, P < 0.001; preterm delivery, K = 0.80, P < 0.001; NICU, K = 0.76, P < 0.001). In sum, antibiotics in infancy was significantly associated with increased risk of EoE diagnosed in adulthood, while positive trends were seen with other early life factors such as Cesarean delivery, preterm delivery, and NICU admission. This may indicate persistent effects of early life exposures and merits additional study into conserved pathogenic mechanisms.© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.