Introduction: In the most recent updated AJCC Cancer Staging Manual for Esophageal and Esophagogastric cancers (Rice, Dis Esophagus 2016; 29(8): 897-905), grade is incorporated for prognosis based on the risk adjusted survival estimates from an international cohort of 13,300 patients who had no preoperative therapy. This study was performed to determine the effect of tumor grade on prognosis in a single institutional experience to evaluate the effect of histologic grade on patients treated with neoadjuvant therapy. Methods: An IRB-approved database was queried to evaluate the effect of tumor grade on prognosis in patients with esophageal cancer at our institution. A database of 1200 patients with clearly defined preoperative grade based on initial biopsy was utilized to investigate tumor grade in relation to demographics, stage, neoadjuvant therapy, resection designation, and survival. Resected patients had a tumor grade of 1-3. Analysis including chi-square analysis was performed to explore if there was an association between grade and prognosis and Kaplan-Meier curves were created to assess overall survival among patients with different tumor grades. Results: Of the 1200 patients in the database, 492 were noted to have clearly-defined grade 1, 2, or 3 surgical specimens upon surgical resection of esophageal cancer and 238 had grade 1 and 3. The cohort was predominantly male (84%) and the mean age was 63.8y. For our analysis, we specifically compare patients who were either grade 1 or grade 3 at diagnosis. There was no significant difference between the groups for age at diagnosis (P=0.763). There was a significant association between tumor grade and both stage (P=0.004) and receipt of neoadjuvant treatment (P=0.000), as patients with stage 1 disease were much less likely to receive neoadjuvant chemotherapy than those with stage 3 disease. Tumor grade was not significantly associated with treatment response (P=0.551), negative margin resection (P=0.252), disease recurrence (P=0.307), and Overall Survival time (P=.232) between patients with low grade(1) and patients with high grade(3) disease. Conclusion: Based on our findings, there is no statistically significant association between pathologic tumor grade and surgical margins, treatment response, recurrence, or survival time. This is in contrast to prior data and warrants further evaluation.