Several esophageal resection techniques have been reported in literature. The objective of this study is to assess postoperative and oncological outcomes of two-stage minimally invasive esophagectomy (MIE) in a prone position using thoracoscopic hand-sewn anastomosis. Consecutive patients who underwent two-stage MIE in 2016 performed by the senior author were included. This was compared with the preceding cohort of consecutive patients who underwent two-stage hybrid esophagectomy (HE). The primary outcome was 30-day morbidity and mortality. The secondary outcomes were operation duration, length of stay (LOS), total nodes examined (TNE), number of positive nodes (NPN), and resection margin. Overall, 15 patients underwent MIE and 11 patients underwent HE. Respiratory complications occurred in three (20.0%) patients in the MIE group and in five (45.5%) patients in the HE group (P = 0.218). Cardiac complications occurred in two (18.2%) patients, and two other patients (18.2%) experienced anastomotic leak in the HE group. Mean operative duration was 349 ± 41.6 min in MIE and 309 ± 47.8 min in HE (P = 0.040). Median LOS was 10 days (range: 7-70) in MIE and 13 days (range: 10-116) in HE (P = 0.045). Median TNE was 23 (range: 12-36) in MIE and 20 (range: 14-47) in HE (P = 0.775). Longitudinal margin was involved in one patient (9.1%) in HE and no longitudinal margin was involved in the MIE group. Circumferential resection margin was involved in seven patients (46.7%) in MIE and in four patients (36.4%) in HE (P = 0.391). Two-stage MIE using hand-sewn technique is safe and feasible without compromising surgical and oncological outcomes. A multicenter large trial is recommended to confirm these results.