Management of esophageal cancer has evolvedmarkedly in the last two decades. Advances in neoadjuvant treatment combined with refinements in surgical techniques and perioperative care have resulted in better postoperative outcomes and long-term survival. We investigated trends in the outcome of esophagectomy for esophageal cancer over the past 20 years at our high-volume institution. We studied patients who underwent surgery for primary cancer of the esophagus or gastroesophageal junction from 1988 through 2008 (N = 1153). Four study periods (P) were compared: 1988-1993 (P1), 1994-1998 (P2), 1999-2003 (P3) and 2004-2008 (P4). Demographic parameters, tumor characteristics, post-operative morbidity, in-hospital mortality and long-term survival were recorded prospectively and the four periods were compared retrospectively. Squamous cell carcinoma accountedfor 77.4% of the 1153 malignancies. The ratio of squamous cell carcinoma to adenocarcinoma fell from 12.0 to 1.3 during the study period (P1 vs P4, P < 0.001), with aparallel increase in the number tumors of the lower esophagus or gastroesophageal junction. The post-operative mortality and morbidity rates were respectively 5.6% and 42.7% overall and remained stable during the study period. The five-year survival rate among all resected patients improved significantly, from 24.3% to 42.7% (P1 vs P4, P< 0.001). The complete (RO) resection rate was 80.7% overall and increased from 74.1% to 82.1% (P1 vs P4, P < 0.05). The five-year survival rate improved significantly among RO-resected patients, from 32.7 % to 52.3 % (PI vs P4, P<.0001). The proportion of patients who received neoadjuvant treatment (mainly chemoradiotherapy) rose from 46.8% to 66.5%. The completeness of the pathologic response after neoadjuvant chemoradiotherapy correlated with long-term survival (P < 0.001): five-year survival rates among pathologically complete, partial and non responders were 52.1%, 24.8% and 10%, respectively. Short-term outcomes after resection remained stable during the study period and comparedfavorably with those reported by other high-volume institutions. Long-term survival improved significantly. Advances in staging methods andsurgical management, combined with more stringent patient selection and use of neoadjuvant chemoradiation, may explain this progress. More reliable predictors of complete RO resection and of the response to chemoradiation therapy are needed in order to tailor management to the individual patient.