Objective To compare the perioperative and follow-up outcomes following thoraco-laparoscopic versus open Ivor-Lewis esophagectomy for middle to distal esophageal cancer, and to explore the application of thoraco-laparoscopic Ivor-Lewis esophagectomy. Methods The clinical data of 148 patients with middle-todistal esophageal cancer, who were treated with thoraco-laparoscopic (minimally-invasive surgery, MIE group, 80 patients) or open (open surgery, OE group, 68 patients) Ivor-Lewis esophagectomy with two-field lymphadenectomy from March 2014 to May 2016, were retrospectively analyzed. There was no significant difference in gender, age, smoking history, tumor location, tumor size, pathological type or staging between the two groups (P > 0.05). Perioperative outcomes and 2-year follow-up outcomes were compared. Results Compared with the OE group, the MIE group had more lymph nodes dissected, less blood loss, shorter postoperative hospital stay and fewer total complications especially pulmonary complications (P < 0.05). However, the total operation time, especially the time for the thoracoscopic surgery in the MIE group was significantly longer than that in the OE group (P < 0.05). Meanwhile, the hospitalization cost of the MIE group was significantly increased (P < 0.05). Upon 2-year follow-up, there was no significant difference in the incidence of anastomotic stenosis, diaphragmatic hernia, local recurrence, metastasis or survival rate between the two groups (P > 0.05). Conclusions Although thoraco-laparoscopic Ivor- Lewis esophagectomy has a longer operation time and higher hospitalization costs, it is superior to open Ivor- Lewis esophagectomy in terms of control of intraoperative bleeding, postoperative complications and postoperative recovery. The long-term effect of thoraco-laparoscopic Ivor-Lewis esophagectomy is not inferior to open Ivor-Lewis surgery, therefore, it is worthy of clinical promotion.