Response criteria remain controversial in therapeutic evaluation for locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy. We aimed to identify the predictive value of tumor regression grading (TRG) in tumor response and prognosis. Fifty-two patients who underwent neoadjuvant chemotherapy followed by esophagectomy and radical 2-field lymphadenectomy between June 2007 and June 2011 were included in this study. All tissue specimens were reassessed according to the TRG scale. Potential prognostic factors, including clinicopathologic factors, were evaluated. Survival curves were generated by using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors were determined with multivariate analysis by using the Cox regression model. Our results showed that of 52 cases, 43 (83%) were squamous cell carcinoma and 9 (17%) were adenocarcinoma. TRG was correlated with pathologic T(P = 0.006) and N (P < 0.001) categories. Median overall survival for the entire cohort was 33 months. The 1- and 2-year overall survival rates were 71% and 44%, respectively. Univariate survival analysis results showed that favorable prognostic factors were histological subtype (P = 0.003), pathologic T category (P = 0.026), pathologic N category (P < 0.001), and TRG G0 (P = 0.041). Multivariate analyses identified pathologic N category (P < 0.001) as a significant independent prognostic parameter. Our results indicate that histomorphologic TRG can be considered as an alternative option to predict the therapeutic efficacy and prognostic factor for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy.