Centralization of cancer care needs to be based on evidence that regionalization will improve outcomes in a given region. We analyzed outcomes for esophagectomy performed in Florida using the Agency for Health Care Administration database. We determined the risk-adjusted mortality rate for the procedure in low-volume and high-volume centers. From 1997 to 2006, 991 esophagectomies were performed in Florida. The incidence of esophagectomy significantly increased from 1997 to 2001 compared with 2002 to 2006, and the postoperative mortality decreased in the latter time period (odds ratio [OR], 1.87; confidence interval [CI], 1.16-3.03). The risk-adjusted postoperative mortality was significantly lower (OR, 0.54; CI, 0.32-0.92) in high-volume centers (5.1 vs 10.4%). The anastomotic leak rates were 8.2 per cent in both high- and low-volume centers. In the largest population-based study for esophagectomy in Florida, outcomes are better in high-volume centers. These data support the regionalization of esophagectomy to high-volume locations in Florida to reduce procedure-related mortality.