OBJECTIVE: The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. BACKGROUND: Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. METHODS: The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. RESULTS: There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. CONCLUSIONS: In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.