The optimal treatment approach for limited-stage small cell carcinoma of the esophagus remains uncertain, we aimed to evaluate the efficacy and safety of preoperative chemotherapy plus surgery versus upfront surgery in those patients.From June 2001 to June 2015, a total of 280 patients with limited-stage small cell carcinoma of the esophagus were screened from 60 131 esophageal cancer patients. The outcome analysis of those patients who receiving preoperative chemotherapy plus surgery or upfront surgery were conducted. The primary endpoint was overall survival and secondary endpoints included progression-free survival and safety.Out of the 280 patients, 200 were men (71.4%), the median age was 64 years (range,42-75 years), 171 patients (61.1%) patients received preoperative chemotherapy plus surgery, and 109 patients (38.9%) underwent upfront surgery. A pathologic complete response rate of 8.8% was noted in patients who received preoperative chemotherapy. Compared to the upfront surgery group, the preoperative chemotherapy group had a better median overall survival (26.0 months vs. 19.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.51 to 0.92; P = 0.011) and a prolonged progression-free survival (16.0 months vs. 13.0 months, respectively; hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P = 0.039). Postoperative complications and peritreatment mortality were comparable between both groups.Compared to upfront surgery, preoperative chemotherapy plus surgery improves overall survival in patients with limited-stage small cell carcinoma of the esophagus.Copyright © 2021. Published by Elsevier Inc.