Background: Neoadjuvant therapy (NT) prior to esophagectomy has dramatically improved survival in patients with esophageal cancer. Currently, most surgeons will allow 6-12 weeks after NT prior to recommending esophagectomy. Given that complete pathologic response (pCR) correlates to an improvement in survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded NT-surgery timing is not currently well understood. Methods: Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent NT followed by esophagectomy. Patients were divided into 4 time intervals: < 6 wks, 6-12 wks, 3-6 mo, and > 6 mo. Mann-Whitney U, Kruskal Wallis, and Pearson’s Chi-square test were used as appropriate. Survival analyses were performed using the Kaplan-Meier method and p < 0.05 was considered significant. Results: We identified 9,256 patients who received NT followed by esophagectomy. There were 8,053 (87%) adenocarcinomas and N = 1203 (13%) squamous cell carcinomas. 7,858 (84.9%) were male and 1,398 (15.1%) female with a median age was 62 (24-88). R0 resections decreased as the NT-Surgery interval increased: < 6 wks, 6-12 wks, 2-6 mos, and > 6 mos at 93%, 94.1%, 94.1%, and 86.2% respectfully p = 0.004. Additionally, the median lymph nodes harvested decreased as timing increased: 12, 12, 10, and 9 p < 0.001 and the median nodes positive decreased as timing increased 1.5, 1.3, 1.1, and 2.4 p = 0.01. The complete response rates increased as timing increased 15.5%, 20.1%, 22.7%, and 25.8% p < 0.001. However, this improvement in pCR did not translate into an increase in median survival: < 6 wks 40.9 mos, 6-12 weeks 38.5 mos, 3-6 mos 34.8 mos, and > 6 mos 39.8 mos of survival, p = 0.94 90-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, 9.4%, and 16.0%, respectively p = 0.001. Conclusions: Our data demonstrates that patients who have a prolonged NT- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a NT-surgery timing of 6-12 weeks should remain.