Regional lymph node (LN) involvement is one of the most important predictors of survival for patients with esophageal cancer. The current staging classification differentiates only between the presence and absence of LN metastasis. In this study, we examined whether involvement of a higher number of LNs is associated with worse survival among esophageal cancer patients. We identified all patients who underwent operations for node-positive esophageal cancer between 1988 and 2003 from the Surveillance, Epidemiology and End Results cancer registry. Because the number of positive LNs is confounded by the total number of LNs removed, patients were classified into three groups by the ratio of positive-to-total number of LNs removed (LN ratio [LNR]): <or= 0.2, 0.21 to 0.5, and>0.5. Esophageal cancer-specific survival was compared among these groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the relationship between the LNR and survival after adjusting for potential confounders. The study cohort included 838 esophageal cancer patients. Disease-specific survival rates decreased with higher LNR. Five-year disease-specific survival was 30% among patients with an LNR<or=0.2, compared with 16% and 13% for those with LNs of 0.21 to 0.5 and>0.5, respectively (p < 0.001). In stratified and multivariable analyses controlling for age, race, gender, histology, tumor-status, and postoperative radiotherapy, a higher LNR was independently associated with worse disease-specific survival. These data suggest that a higher LNR among patients with node-positive esophageal cancer is associated with worse survival. If validated, this prognostic criterion may be included in staging classifications.