Anastomotic leakage is still the major surgical complication following transthoracic esophagectomy with intrathoracic esophagogastrostomy (Ivor-Lewis procedure). Modifications of this standard procedure aim to reduce postoperative morbidity and mortality. In this retrospective analysis of a 12-year period, 419 patients who had an Ivor-Lewis (IL) procedure for esophageal carcinoma were included. Due to modifications of the standard procedure, two different groups were compared with respect to their mortality and anastomotic leakage rate. In 181 patients (43.1%), esophagectomy and gastric reconstruction was performed as a one-stage procedure (classical IL group). Two hundred thirty-eight patients (56.9%) underwent a modified IL procedure that included minimally invasive gastric mobilization and a two-stage operation following ischemic conditioning of the gastric conduit. The hospital mortality rate was lower in the modified IL group without statistical significance (2.9 vs. 6.1%). Thirty-five anastomotic leaks were diagnosed postoperatively, 17 in the classical IL group (9.4%) and 18 in the modified IL group (7.6%). The rate of late leakages (after the 10th postoperative day) was higher in the modified IL group. Septic complications and mortality following anastomotic leakage were less frequent in the modified IL group. Leaks in the classical IL group predominantly required rethoracotomy, whereas leaks of the modified IL group were sufficiently treated with endoscopic stenting. Surgical modifications of the classical IL procedure, including a minimally invasive approach and ischemic conditioning of the gastric conduit, seem to reduce postoperative morbidity and mortality. However, due to the retrospective design of this study, the impact of other factors influencing the outcome cannot be ruled out.