Abstract Background Esophagectomy is a crucial curative treatment for potentially resectable esophageal cancer. However, anastomotic leakage poses a significant complication, with reported incidences ranging from 11.4% to 21.2% and mortality rates between 7.2% and 35%. Endoluminal or cavitary type of vacuum therapy (EVAC) represents a minimally invasive approach adapted from negative pressure wound closure techniques. Our case demonstrates the successful application of EVAC in managing a significant postoperative leak. Methods A 70-year-old male who underwent esophagectomy for early esophageal cancer. On postoperative day 23, a 20mm-sized large anastomotic leakage was detected, leading to the insertion of Endo-VAC for treatment. Endoscopically exchange was regularly. Results Endoscopically exchange was performed seven times, gradually reducing the size of the leakage hole. In the end, the anastomotic leakage was completely healed, and the patient was discharged on postoperative day 86. The patient id currently undergoing outpatient follow-up with no recurrence or metastasis of the disease confirmed. Conclusion Through our case, we highlight the potential suitability of EVAC therapy as a less invasive and effective treatment modality for anastomotic leakage following esophagectomy. This approach may be considered as a priority treatment for anastomotic leak.