Background Esophageal perforation is a serious disease with a high morbidity and mortality rate. Endoscopic vacuum therapy (EVT) is a new endoscopic treatment option, which is used to treat anastomotic leakages after rectal and esophageal resections. We report on 10 patients treated with EVT for esophageal perforation. Methods Clinical and therapy-related data such as age, sex, duration of intensive care stay, length of hospital stay, reasons for perforation, EVT-associated complications, mortality, need for alternative treatment options, and course of infectious variables were analyzed. Results Ten patients were treated with 54 vacuum sponges that were placed in upper gastrointestinal defects. Causes for perforation were iatrogenic, spontaneous, or foreign body-associated. Mean number of sponge insertions was 5.4 (range, 2 to 12) with a mean period of 19 ± 14.26 days. Successful therapy was achieved in 9 of 10 patients. After successful primary treatment, 1 patient died during therapy as a result of general failure of the cardiovascular system. In 1 patient, surgical resection was necessary after repeated Mallory-Weiss lesions and minor perforations during the course of immunosuppressive therapy. In a third patient an endoscopic stent was inserted in the clean wound cavity after primary EVT. Conclusions In this small trial EVT has been shown to be a safe and feasible therapy option for perforations of the upper gastrointestinal tract. If necessary, EVT can be combined with operative revision for better control of the local septic focus or used as a bridging procedure for wound conditioning before aggressive surgical treatment.