Background: Esophageal cancer is surgically treated by means of an esophagectomy. However, esophagectomies are associated with high morbidity rates with dehiscence of the anastomosis occurring in 19% of these procedures in the Netherlands. Application of a fibrin sealant may improve mechanical strength of the anastomosis. The aim of this study was to determine the technical feasibility of the application of an autologous fibrin sealant by aerosolized spraying on esophageal anastomoses. Methods: This study was designed as a single-center feasibility study. Patients undergoing elective minimal invasive esophageal surgery with the creation of a thoracic or a cervical anastomosis were eligible. Fibrin sealant (Vivostat) was applied to the anastomosis intraoperatively. Feasibility was measured using a nine-item checklist, designed for intraoperative application. Results: In total, fifteen patients, between the ages of 43-79 y, were included in this study. One procedure scored eight out of nine points on the feasibility checklist, so application was considered as unsuccessful. The other fourteen procedures obtained a 100% score and were documented as successful procedures. Together, this led to a success rate of 93%. Grade III anastomotic leakage occurred in one of the fifteen patients (6.7%). Conclusions: This study showed that application of fibrin sealant on esophageal anastomoses is technically feasible and safe. Future studies may investigate the possible protective effects of fibrin sealant application on the development of anastomotic leakage. NCT03251040.