PURPOSE: To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. MATERIALS AND METHODS: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) (42~46 Gy) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to 54~66 Gy, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, 9~12 Gy/3~4 fx). Two cycles of concurrent FP chemotherapy (5-FU 1,000 mg/m2/day, days 2~6, 30~34, cisplatin 60 mg/m2/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. RESULTS: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range 1~149 months)]. The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range 44.4~66) and a total radiation dose, including BT, of 60 Gy (range 44.4~72), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29.0% at 2 years and 22.7% at 5 years (median 10.4 months). The response to treatment and N-stage were significant factors affecting overall survival. In addition, total radiation dose (> or =50 Gy vs. <50 Gy), BT and fractionation scheme (qd. vs. bid.) were not significant factors for overall survival and disease-free survival. CONCLUSION: Survival outcome after definitive chemoradiation therapy in unresectable esophageal cancer was comparable to those of other series. The main failure pattern was local recurrence. Survival rate did not improve with increased radiation dose over 50 Gy or the use of brachytherapy or hyperfractionation.