Background <p>The prognostic significance of sex and age-sex in patients with esophageal carcinoma (EC) remains unclear. This study aimed to clarify whether the sex or age-sex factor influences the prognosis of patients with EC after esophagectomy.</p> Methods <p>The data were sourced from an original database, which includes data on patients with EC who had undergone esophagectomy between 2012 and 2016 at a high-volume cancer center. The cut-off age in our study was 55 years. Based on age and sex, the patients were categorized into the following four groups: Group A, comprising women aged&#xa0; &lt; 55 years; Group B, women aged ≥ 55 years, Group C, men aged&#xa0; &lt; 55 years; and Group D, men aged ≥ 55 years. Cox regression analysis was used for multivariate analysis. Propensity score matching (PSM) was used to adjust for the confounding factors.</p> Results <p>A total of 1576 patients was included. The 5-year OS rates for groups A, B, C, and D were 59.0%, 53.2%, 42.4%, and 45.4%, respectively, with statistically significant differences between them (<i>P</i> &lt; 0.001). The multivariable Cox regression analysis revealed that age-sex groups, adjuvant therapy, and pTNM stage were independent prognostic factors. Following PSM, the results demonstrated that younger women with EC had a significantly better prognosis than did patients in other age and sex cohorts (hazard ratio [HR]: 0.368, 95% confidence interval [CI]: 0.203–0.666).</p> Conclusion <p>Compared with other patients, younger women with EC had a significantly better prognosis after esophagectomy.</p>