Background: Esophageal cancer (EC) is increasing in incidence dramatically, and is associated with suboptimal outcomes despite the widespread adoption of neoadjuvant multimodality therapy (NAT) as a de-facto standard-of-care for clinically resectable disease. Between one-quarter and one-third of patients (pts) are found to have no evidence of tumor (pCR) at the time of surgical resection, a prognostic indicator of superior survival benefit. However, we currently lack a method to prospectively identify pts who will respond to (NAT). Identifying complete responders could reduce the number of patients requiring esophagectomy. The specific aim of this study was to determine if the pre-operative neutrophil to lymphocyte ratio (NLR), which has been reported as a prognosticator of mortality, is prognostic of pCR to NAT. Methods: A prospectively collected database was queried for all pts that have undergone esophagectomy for EC, including both squamous cell carcinoma and adenocarcinoma. Records were evaluated for preoperative complete blood count (CBC) with differential from which a NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. A NLR greater than 5 was considered elevated. Pts were classified as pCR if they had no residual tumor on final pathology, partial responders (PR) if they demonstrated down staging after neoadjuvant therapy, or non-responders (NR) if they did not show any improvement in their stage on final pathology. Results: Of 114 pts who underwent both NAT and esophagectomy for EC, 41 had a pre-operative CBC with differential from which a NLR could be calculated. There were 19 NR, 14 PR and 8 CR. These groups were demographically similar. The average NLR was 5.92 for NR, 6.56 for PR, and 4.89 among CR, with no statistically significant difference between groups. Overall survival at 5 years was 33%. By multivariate analysis NLR>5 did not correlate with pathologic response (p=0.78), and NLR >5 did not correlate with survival (p=0.33). Conclusions: Elevated neutrophil to lymphocyte ratios are not predictive of pathologic response to NAT in esophageal cancer.