Background: Esophageal cancer (EC) is historically a male-predominant disease. Current available evidence on the impact of gender on clinical presentation and survival outcomes of EC is limited by small sample size or single institutional series. Methods: Patients with EC (stage I-III) were identified in the National Cancer Data Base (NCDB, 2004-2016). Clinicopathologic and treatment characteristics of male and female patients were compared using Chi-square analysis. Overall survival (OS) was estimated using Kaplan-Meier method and Cox proportional hazards regression. Results: Of 62,893 patients included, male gender was predominant (77.7% vs 22.3%). Adenocarcinoma was the most common subtype (66.7%); however, squamous cell carcinoma was more predominant in females (57.1% vs. 26.5%, p<0.001). Females were significantly older (68.5 vs. 66.1 years; p<0.001) and more likely African American (AA) (14% vs. 8.1%; p<0.001). Females were more likely to present with local disease (stage I, 19.6% vs. 18.2%; p<0.001), while males presented more likely with locoregional disease (LRD, stage II/III, 80.4% vs 81.8%, p<0.001). Females had worse OS compared to males (18.1 vs. 19.7 mo; p=0.001; cI: 23.5 vs. 31.9mo, p<0.001; cII/III: 17.2 vs 18.3mo, p=0.473). White females had worse OS than white males (18.6 vs. 20.4mo, p<0.001), while AA females had better OS (13.5 vs. 12.6mo, p=0.001). Among patients with LRD, females less frequently received chemotherapy (CT, 75.4% vs. 82.9%, p<0.001), radiation therapy (RT, 78.9% vs. 82.6%, p<0.001), and esophagectomy (28% vs. 40.5%, p<0.001). Females who underwent esophagectomy had improved OS over males (40.3 vs. 32.7mo; p<0.001). More specifically, white females who underwent esophagectomy had improved OS over white males (47.6 vs 38mo, p<0.001); however, AA males and females who underwent esophagectomy had similar OS (33.8 vs 32.6mo, p=0.452). Female gender, advanced age, AA race, high comorbidity score and clinical stage, and lack of access to CT, RT, and esophagectomy were independent predictors of mortality (Table). Conclusions: Females with EC seem to have less access to CT, RT and esophagectomy, which is associated with worse OS compared to males. Healthcare policies should be implemented to increase access to standard of care treatment for female patients with EC.