Neoadjuvant therapy improves long-term locoregional control and overall survival after surgical resection for esophageal cancer, and neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) are commonly used in clinical practice. Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR), the efficacy of nimotuzumab added to nCRT for esophageal cancer is uncertain. We conducted this retrospective study in which combining neoadjuvant treatment of nimotuzumab with chemoradiotherapy (Nimo-nCRT) is compared with nCRT and nCT for patients with potentially resectable locally advanced esophageal squamous cell carcinoma. One hundred ninety-five patients received neoadjuvant therapy and 172 (88.2%) underwent esophagectomy. Surgical resection was performed in 94.4% after Nimo-nCRT, versus 92.5% after nCRT and 83.5% after nCT (P = 0.026). The R0 resection rate was 100% after Nimo-nCRT, 95.9% after nCRT and 92.6% after nCT (P = 0.030). Pathological complete response (pCR) was achieved in 41.2% after Nimo-nCRT, versus 32.4% after nCRT and 14.8% after nCT (P = 0.0001). Lymph-node metastases were observed in 29.4% in the Nimo-nCRT group, versus 21.6% in the nCRT group and 35.8% in the nCT group (P = 0.093). More patients in the Nimo-nCRT and nCRT group developed grade 3 esophagitis compared to those in the nCT group, P = 0.008. There was no difference in surgical complications between the treatment groups. nCRT results in improved R0 resection, higher pCR rate, and a lower frequency of lymph node metastases compared to nCT, adding nimotuzumab to nCRT is safe and appears to facilitate complete resection and increase the pCR rate.