Abstract Aim To report the prospective experience in Hybrid Laparoscopic Robot-assisted Minimally-invasive Esophagectomy (HLRAMIE) in a referral Center. Background & Methods The minimally-invasive esophagectomy (MIE) is an attractive and established technique to improve the reduction of post-operative morbility with sound oncological results. The hybrid combination of laparoscopy and full robotic thoracic phase (HLRAMIE) is an approach aimed to be as effective as MIE to treat esophageal neoplasms. Inclusion criteria: patients undergone to multimodal medical advice panel, affected from non-cT4, from mid thoracic to cardia, esophageal neoplasms, with and without neoadjuvant treatment, fit for minimally-invasive surgery. HLRAMIE: laparoscopic stage plus full robotic thoracic stage by Da Vinci Xi® (Intuitive Surgical, US), with gastric-pull first-choice conduit. Prospective, dedicated database. Results From October 2015 to April 2019, 33 patients underwent to HLRAMIE (site of neoplasm: 1 mid thoracic; 9 inferior; 23 cardia). 5 out 33 were converted to open. 27/28 underwent to a Ivor Lewis esophagectomy, 1/28 to McKeown procedure. The mean total surgical time was 517 minutes, mean robotic docking time 12 min with mean thoracic time 269 min (positive trend). Gastric pull-up was performed in 28/28. In 23/28 patients the esophago-gastric anastomosis was performed full robotic after the fashion of hand, in 5/28 was performed by circular stapler. The mean extubation time was 12 hours. The mean number of lymph node removed was: overall fields 32.4 (range 15-58), thorax 9.8 (3-27). The mean number of metastatic lymph node was 3.8 (0-18). 100% were R0 resections. The mean hospital-stay was 15 days. The perioperative mortality and 30-day mortality were both 0%. The overall post-operative morbility was 32.1%. 4/28 (14.2%) patients developed an anastomotic leakage, 75% were managed by endoscopy. 11/28 (39.2%) patients developed a late anastomotic stenosis (all in the hand made group). Conclusion In our experience, HLRAMIE is surgically reproducible with the principle of learning curve; oncologically adequate in relation to radical dissection; safe and effective in relation to post-operative early morbility and mortality. Long-term follow up and more powerful, randomized series are needed to establish the definitive clinical and oncological results of HLRAMIE.