The effect of neoadjuvant chemotherapy on the survival of patients with thoracic esophageal squamous cell carcinomas (ESCCs) remains controversial. The optimal management strategy for resectable ESCCs varies regionally based on local randomized controlled trials. A systematic review and meta-analysis was conducted to re-evaluate this controversial issue.A systematic review of the Medline, Embase, and PubMed databases was carried out on data collected between August 1994 and August 2014 to evaluate the role of neoadjuvant chemotherapy. Only randomized controlled trials comparing the effects of neoadjuvant chemotherapy with that of surgery and surgery plus adjuvant chemotherapy were selected.Six studies with a total of 1202 patients were identified, consisting of a neoadjuvant chemotherapy arm (n = 597) and a surgery alone and surgery plus adjuvant chemotherapy arm (n = 605). The 5-year overall survival benefit for neoadjuvant chemotherapy was statistically significant at α = 0.1 (hazard ratio = 0.81, 95% confidence intervals, 0.65-1.00, P = 0.053). All 6 trials recruited patients for more than 5 years with undefined lymphadenectomies. Cisplatin and fluorouracil were adopted as neoadjuvant chemotherapy regimens.The role of neoadjuvant chemotherapy for ESCC is worth re-investigating. The design of randomized controlled trials should adopt new chemotherapy regimens as well as define the surgical procedure and the details of the lymphadenectomy.