BACKGROUND: Anastomotic leakage (AL) contributes to postoperative morbidity and mortality after Ivor-Lewis esophagectomy. Vascular high-risk patients show a significantly increased risk of AL. We previously showed that laparoscopic ischemic conditioning (ISCON) of the stomach prior esophagectomy in these high-risk patients is a safe procedure that induces neoangiogenesis at the anastomotic site. Our data also suggested that this directly impacts on anastomotic healing. To further investigate the hypothesis that gastric conduit vascularization directly influences postoperative morbidity, we evaluated gastric conduit vascularity in a cohort of patients undergoing two-stage esophagectomy prior to the ISCON era. MATERIAL AND METHODS: Seventy-nine patients who underwent two-stage esophagectomy from 2016 to 2021 at our center were retrospectively analyzed from a prospectively maintained database. Microvessel density (MVD) of the gastric conduit at the anastomotic region was evaluated by CD34 staining of the gastric stapler ring. Analysis of microvessel density (MVD) was performed using ImageJ. Patients were stratified into low- and high-MVD groups, and MVD was correlated with clinical outcomes. RESULTS: Patients with a high MVD showed a significantly lower rate of anastomotic leakage (AL) in comparison to patients with low MVD (6.25% vs. 22.58% p=0.043). Furthermore, a high MVD was associated with a lower rate of major complications (Clavien Dindo ≥ IIIb) (12.50% vs. 38.71% p=0.012) and a shorter hospital stay (17.9 days vs. 23.1 days, p=0.045). CONCLUSION: Vascularization of the stomach might function as surgical biomarker of AL in patients undergoing two-stage esophagectomy. Prospective trials have to further substantiate this finding.