Background: This multicenter phase II trial assessed the safety and efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (IC) and subsequent conversion surgery (CS) for locally advanced unresectable esophageal cancer (LAUEC). Methods: Esophageal cancer patients (pts) with clinical T4 disease and/or unresectable supraclavicular lymph node metastasis were eligible. The treatment starts with 3 cycles of DCF-IC, followed by CS if resectable, or by concurrent radiation plus chemotherapy with 5-fluorouracil and cisplatin (CF-RT) if not resectable. In case of CF-RT, the resectability is re-evaluated at 30 Gy-40Gy, followed by CS if resectable, or by additional CF-RT with total irradiation dose of 60Gy. If resectable after completion of CF-RT, CS is performed. The primary endpoint is 1-year overall survival (OS). We assumed a null hypothesis with 50% and expected 65% of 1-year OS. Results: Characteristics of 48 pts enrolled were as follows: median age, 66 years; PS0/1, 28/20; primary tumor sites, Ut/Mt/Lt, 13/33/2; T3/T4a/T4b, 5/1/42; N0/N1/N2/N3, 4/12/22/10; M0/M1, 39/9. Eleven pts (22.9%) developed febrile neutropenia related to DCF-IC. CS was performed in 20 pts (41.7%), including DCF-CS (n = 18), DCF-CF-RT40Gy-CS (n = 1), and DCF-CF-RT60Gy-CS (n = 1). R0 resection was confirmed in 19 pts (39.6%). Grade ≥ 3 postoperative complications includes 1 recurrent laryngeal nerve palsy, 1 lung infection, 1 wound infection, 1 pulmonary fistula, and 1 dysphagia; but no remarkable postoperative complications were observed in pts who underwent CS. The overall cure rate including R0 resection or the clinical complete response after CF-RT was 47.9%. The estimated 1-year OS was 67.7% and lower limit of 80% confidence interval was 59.5%. The OS for pts who underwent R0 resection was significantly longer than those who did not undergo R0 resection (median survival time: not reached vs. 326 days, p < 0.01). There was 1 treatment-related death in patient who received DCF-CF-RT60Gy. Conclusions: DCF-IC followed by CS showed promising signs of tolerability and efficacy in pts with LAUEC. Clinical trial information: 000011089.