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The value of adding induction chemotherapy (ICT) to preoperative chemoradiotherapy followed by surgery has not been delineated well.Patients with stage II, III or IVA (by AJCC 6th ed.) esophageal cancer were randomly allocated to either two cycles of ICT (oxaliplatin 130 mg/m2 on day 1 and S-1 at 40 mg/m2 bid on days 1–14, every 3 weeks), followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/day with oxaliplatin 130 mg/m2 on day 1 and 21 and S-1 30 mg/m2 bid, 5 days/week during radiotherapy) and surgery (arm A, n = 48), or the same chemoradiotherapy followed by surgery without ICT (arm B, n = 49). The primary outcome was to compare pathologic complete response (pCR).Thirty-six and 35 patients underwent surgery with or without ICT, respectively. The pCR rate among those who underwent surgery was significantly lower in arm A (30.6% versus 54.3%, P = 0.043). However, no difference in progression-free survival (PFS) and overall survival (OS) was observed with a median follow-up of 19.5 months (95% CI, 19.1–22.4). The 2-year PFS rate was 63.8% in arm A and 55.2% in arm B (P = 0.626) and 2-year OS rate was 70.1% and 62.6%, respectively (P = 0.515). While 47 (arm A) and 48 (arm B) patients received at least 44 Gy of radiotherapy, relative dose intensity (RDI) for oxaliplatin during CCRT was significantly lower in arm A versus arm B (92.7% ± 19.6% versus 99.7 ± 1.8%, P = 0.017). RDI for S1 did not significantly differ (94.1% ± 17.3% versus 98.5% ± 5.9%, P = 0.095). G3/4 thrombocytopenia was significantly common in arm A (37.5% versus 4.1%, P < 0.001), which contributed to lower RDI of oxaliplatin. Three patients in arm A, compared with none in arm B, failed to survive for 90 days after surgery.Adding this ICT to preoperative chemoradiotherapy seems to cause lower pCR rate and higher toxicity during CCRT.