Esophagectomy, one of the most invasive of all gastrointestinal operations, is associated with a high frequency of postoperative complications and in-hospital mortality. The purpose of the present study was to determine whether exposure to the atomic bomb explosion at Hiroshima in 1945 might be a preoperative risk factor for in-hospital mortality after esophagectomy in esophageal cancer patients. We thus reviewed the outcomes of esophagectomy in 31 atomic bomb survivors with esophageal cancer and 96 controls (also with cancer but without atomic bomb exposure). We compared the incidences of postoperative complications and in-hospital mortality. Of the clinicopathological features studied, mean patient age was significantly higher in atomic bomb survivors than in controls. Of the postoperative complications noted, atomic bomb survivors experienced a longer mean period of endotracheal intubation and higher incidences of severe pulmonary complications, severe anastomotic leakage, and surgical site infection. The factors associated with in-hospital mortality were exposure to the atomic bomb explosion, pulmonary comorbidities, and electrocardiographic abnormalities. Multivariate analysis revealed that exposure to the atomic bomb explosion was an independent significant preoperative risk factor for in-hospital mortality. Exposure to the atomic bomb explosion is thus a preoperative risk factor for in-hospital death after esophagectomy to treat esophageal cancer.