The aim of this study is to develop a prognostic nomogram, quantify survival benefit, and guide risk-dependent adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) after esophagectomy.This was a single-center, retrospective study of consecutive LA-ESCCs treated by curative-intent esophagectomy with internal validation and independent external validation in a randomized controlled trial. After factor selection by the least absolute shrinkage and selection operator regression, a nomogram was developed to estimate 5-year overall survival (OS) based on the Cox proportional hazards model. The area under the curve (AUC) and calibration plot were used to determine its discriminative and predictive capacities, respectively. Survival improvement from adjuvant therapy was quantified and plotted corresponding to nomogram score.A total of 1077, 718, and 118 patients were included for model development, internal validation, and external validation, respectively. The nomogram identified eight significant prognostic factors: gender, pathological T and N stages, differentiation, surgical margin, lymphovascular invasion, number of lymph node resection, and adjuvant therapy. The nomogram showed superior discriminative capacity than TNM stage (AUC: 0.76 vs. 0.72, p < 0.01), with significant survival differences among different risk stratifications. The calibration plot illustrated a good agreement between nomogram-predicated and actual 5-year OS. Consistent results were concluded after external validation. At least 10% 5-year OS improvement from adjuvant chemoradiotherapy and chemotherapy was expected in almost all patients (nomogram score 110 to 260) and patients mainly with high-intermediate risk (nomogram score 159 to 207), respectively.The clinicopathological nomogram predicting 5-year OS for LA-ESCC after esophagectomy was developed with high accuracy. The proposed nomogram showed better performance than TNM stage and provided risk-dependent and individualized adjuvant treatment recommendations.