Background: Esophageal cancer survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy for patients who present with locally advanced disease. Unfortunately, overall prognosis for these patients remains poor. In this study, we sought to assess the effect of additional adjuvant chemotherapy in patients who have positive lymph nodes (pN+) following surgery. Methods: Using the National Cancer Database we retrospectively identified all patients with locally advanced esophageal cancer who received neoadjuvant CRT from 2004 to 2014. We then identified patients within this dataset who were found to be pN+ following neoadjuvant chemoradiation and esophagectomy and categorized them as having received adjuvant chemotherapy versus no additional chemotherapy. Survival analysis was performed using Kaplan-Meier estimation and propensity score matching. Results: 2,045 patients were identified as being pN+ following neoadjuvant CRT. Within this group, 14% received adjuvant chemotherapy. The 1, 5, and 8 year overall survival (OS) of patients receiving adjuvant therapy was 87%, 30%, and 21% compared to 76%, 23%, and 16% in those receiving neoadjuvant therapy alone, respectively (p = 0.0017). After a propensity score matched analysis, median OS was found to be significantly longer in the those receiving neoadjuvant CRT plus adjuvant chemotherapy compared to neoadjuvant CRT alone (27.8 months vs 22.2 months; HR 0.78; 95% CI, 0.62 to 0.97; p = 0.032). Conclusions: While not currently the standard of care, our data suggests that adjuvant chemotherapy may improve survival in patients with locally advanced esophageal cancer who are found to be pN+ following surgery. Additional prospective studies are needed to confirm this finding.