Objective: To evaluate the safety and availability of totally minimally invasive Ivor-Lewis esophagectomy (MIIE) with single-utility incision video-assisted thoracoscopic surgery. Methods: Forty-eight patients with middlelower thoracic esophageal cancer were prospectively treatment with MIIE from February 2013 to February 2014 at Fudan University Shanghai Cancer Center, the first 36 patients who were treated with esophagectomy by four-port VATS, while the others were treated with single-utility incision VATS. Clinicopathological parameters were examined, including conversion to open, average operative duration, average operative blood loss, blood transfusion, postoperative hospital stay, postoperative ICU stay, average thoracic lymph node yield, average abdominal lymph node yield postoperative morbidity, pathological staging and operative complications. Results: The operations were carried out successfully in two groups, there was no perioperative death in all patients. There was no statistical difference in the case number of conversion to open, average operative duration, average operative blood loss, blood transfusion, postoperative hospital stay, postoperative ICU stay, average thoracic lymph node yield, average abdominal lymph node yield postoperative morbidity, pathological staging and operative complications between the two groups. Conclusion: MIIE with single-utility incision video-assisted thoracoscopic surgery is technically feasible and safe in patients with mid-lower thoracic esophageal cancer with minimized trauma. The recent result is satisfactory.