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Several population-based studies have shown that the total number of surgically removed lymph nodes is independently associated with overall and disease-free survival in a variety of gastrointestinal cancers. In this retrospective study, the impact of total nodal count on overall survival in esophageal cancer was examined using a single institution surgical database.We conducted a retrospective review of 264 patients with esophageal cancer treated by esophagectomy without neoadjuvant therapy between January 1988 and December 2006. The association between overall survival (the primary endpoint) and the total number of dissected lymph nodes was evaluated using multivariable Cox regression models.When the total number of resected nodes was examined as a categorical variable based on quartiles (category 1: ≤16, category 2: 17–25, category 3: 26–40, category 4: >40) there was a reduced hazard of death with increasing number of examined nodes. Compared with those in category 1, the death hazard was reduced by 34% (P = 0.08), 48% (P = 0.001), and 49% (P = 0.001), respectively, for patients in categories 2, 3, and 4. For node negative patients a significantly reduced hazard was present only when more than 40 nodes were resected (HR = 0.23, P = 0.01). For node positive patients the death hazard was significantly reduced for those in all higher categories compared with those in category 1 (HR = 0.53, 0.39, 0.49; P = 0.03, 0.001, 0.02, respectively).These data support the findings from population based studies in esophageal cancer and other gastrointestinal tumors, suggesting that a higher nodal count favorably influences survival.