The relationship of complete pathologic response (cPR) with the timing of esophagectomy after neoadjuvant chemoradiation (nCRT) is not well defined. We sought to determine if a delay in esophagectomy after nCRT would result in increased likelihood of cPR and improved survival. This is a retrospective analysis of a prospectively maintained database of all patients treated with nCRT and esophagectomy between 2004 and 2014. Patients were divided into two groups based on timing of esophagectomy (≤50 vs. >50 days) after completion of nCRT. Survival outcomes were compared using standard Kaplan-Meier curves, and multivariable analyses were performed using Cox regression models. This study included 226 patients (males, 211 and median age, 61 years) for analysis. Fifty-two patients (23%) in the early group (≤50 days) were compared to 174 patients (77%) in the delayed group (>50 days). The two groups were similar with respect to age, gender, comorbid conditions, ECOG status, location, grade, and tumor histology. There was no statistically significant difference in cPR rate between the early and late groups (26.9% vs. 19.0%, respectively, P=0.24). On multivariable analysis, lower age, absence of signet cell histology, better ECOG status, shorter length of stay and cPR were independent predictors of improved survival. The median follow-up was 52 months (range, 2-110 months), and there was no difference in the median overall survival (OS) between the early and late groups (48.9 vs. 42.6 months, respectively, P=0.73). This analysis of a large cohort of patients with esophageal cancer undergoing multi-modality therapy shows that cPR is independent of the timing of esophagectomy. Other considerations for the timing of surgery, including recovery from nCRT and patient performance, may have more relevant roles than cPR when deciding when to perform esophagectomy.