Background: The optimal time interval from neoadjuvant chemoradiotherapy (nCRT) to surgery remains controversial in esophageal cancer (ESC) patients. Hence, this study aimed to evaluate the relationship of the time interval from nCRT to surgery with the prognosis in ESC patients. Methods: Totally, 166 ESC patients treated with nCRT followed by surgical resection were reviewed. Their pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) were analyzed. Based on the median duration from nCRT to surgery, patients were classified into duration from nCRT to surgery ≥66 days group or <66 days group. Results: The pCR rate was elevated in duration from nCRT to surgery ≥66 days group compared to <66 days group (48.3% vs. 25.3%, P = 0.002), while DFS (P = 0.316) and OS (P = 0.883) were of no difference between these two groups. The duration from nCRT to surgery (≥66 days vs. <66 days) (odds ratio (OR): 2.149, P = 0.039) was independently related to improved pCR rate as validated by multivariate logistic regression, while it did not correlate with DFS or OS (both P> 0.05) by univariate and multivariate Cox’s regression analyses. Moreover, female gender (P=0.001) and radiation dose ≥40 Gy. (P = 0.039) could independently predict better pCR rate; and pCR rate was independently related to longer DFS (P = 0.003) and OS (P = 0.008). Conclusions: The prolonged time interval from nCRT to surgery relates to a higher pCR rate but does not correlate with DFS or OS in ESC patients.