Background: There are indications that robot-assisted minimally invasive esophagectomy (RAMIE) can reduce the morbidity compared with the conventional operative technique. Objective: A comparative analysis of a single-center change in strategy of the standard from open esophagectomy to RAMIE with perioperative, enteral, selective bowel decontamination (SBD) was carried out. Material and methods: Patient and morbidity data after elective RAMIE treated according to the novel standard management between July 2018 and September 2020 were compared retrospectively with an historical control cohort after open esophagectomy between January 2014 and June 2018. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 75 patients could be analyzed in both groups after PSM. Approximately two thirds of the operations were carried out due to an adenocarcinoma and one third due to a squamous cell carcinoma. The median number of resected lymph nodes was 22 and 21, respectively. In the RAMIE group the intrathoracic esophagogastrostomy was performed using a circular stapler with a diameter of ≥28 mm in 97%, whereas a 25 mm stapler was used in 90% in the control group. The operative time was longer (median 490min vs. 339 min, p < 0.001) but in contrast blood loss (median 300ml vs. 500 ml, p < 0.001), anastomotic leaks (8.0% vs. 25.3%, p = 0.004), surgical site infections (4.0% vs. 17.3%, p = 0.008) and pulmonary complication rates (29.3% vs. 44.0%, p = 0.045) as well as the median hospital stay (14 days vs. 20 days, p < 0.001) and 90-day mortality were significantly reduced compared with the open control group (4.0% vs. 13.3%, p = 0.039). Conclusion: A consistent change of the perioperative management including RAMIE and SBD can lead to a stable reduction of morbidity without compromising oncological radicalness.