Background: Definitive chemoradiotherapy is associated with high local treatment failure rates, and surgical resection may be an appropriate salvage therapy. However, the efficacy and safety of salvage esophagectomy have not been elucidated fully. The clinical outcomes of salvage esophagectomy for locoregional failure after chemoradiotherapy were assessed. Methods: Twelve patients who underwent salvage esophagectomy after chemoradiotherapy between January 2003 and November 2010 were included in this retrospective analysis. Baseline demographics and survivals of these patients were compared with 21 patients who did not receive salvage esophagectomy for locoregional failure only after chemoradiotherapy, identified from our own previous prospective trials. Results: The median age was 62.5 years (range 50 to 69) and all patients had squamous cell carcinoma. The median radiation dose was 54.0 Gy (range 41.4 to 66.0) and the median interval between completion of chemoradiation and surgery was 8.0 months (range 2.0 to 32.9). There were no in-hospital deaths. Pulmonary complication was the most common postoperative morbidity (42%), and anastomotic leakage occurred in 1 patient (8%). With a median follow-up period of 29.3 months (range 5.8 to 73.0), the overall 3-year survival rate was 58%. Patients with early pathologic stage disease (T1/2 and N0) showed significantly prolonged survival (p = 0.03) compared with those with advanced pathologic stage (T3/T4 or N1). Patients with salvage esophagectomy had prolonged event-free survival and overall survival compared with those patients with locoregional failure who received primary chemotherapy or boost radiotherapy (p < 0.001). Conclusions: While salvage esophagectomy for locoregional failure after chemoradiotherapy should be employed with great caution, it appears to be a feasible and effective therapeutic option for highly selected patients, especially with early pathologic stage disease. Salvage esophagectomy can be recommended as the only current curative treatment option for patients with locoregional failure after chemoradiotherapy.