Background: Eosinophilic esophagitis (EoE) is a male predominant disease, typically presenting with dysphagia. Our goal was to investigate sex differences in clinical presentation and management of EoE. Methods: We performed a retrospective cross-sectional review of 489 EoE patients seen at NewYork Presbyterian Weill Cornell from August 2015 to August 2019. Charts were queried for age at diagnosis, symptoms at presentation, endoscopic findings, need for dilations, and medical therapy. Student t and χ² tests were implemented to compare outcome variables of the 2 independent groups (males vs females) and logistic regressions for invariable and multivariable analyses. Results: 489 EoE patients (226 Female [F] [46.2%], 263 Male [M] [53.8%]) were reviewed. Males were more likely to present with food impaction (92 [35.8%] vs 44 [19.7%], M vs F, P < .001), have a fibrostenotic phenotype on initial endoscopy (140 [54.1%] vs 98 [45.0%], M vs F, P = .043) and undergo dilation (odds ratio [OR] = 1.985, 95% confidence interval [CI] = 1.209-3.328, P < .01). Female patients were more likely to have atopic disease (153 [67.6%] vs 153 [58.8%], F vs M, P = .044) and a reported normal index endoscopy (79 [36.2%] vs 69 [26.6%], F vs M, P = .026). Conclusion: This large retrospective review highlights clinically important differences in presentation between sexes. Increasing awareness of these differences, especially history of atopic disease, impaction, and the need for dilation, can help clinicians better identify EoE in female patients and therefore, guide initial therapy. The mechanistic underpinnings of these discrepancies are not evident from this data and will require future studies.