Endoluminal resection in the gastrointestinal tract is limited to resection of the lamina mucosa and lamina submucosa. The integrity of the gastric wall, represented by the lamina muscularis propria, must be maintained, because no safe endoscopic methods of ensuring adequate closure of the gastric wall are currently available. With the flexible stapling system SurgAssist (Power Medical Interventions ([Power Medical Interventions Deutschland GmbH, Hamburg, Germany]), for the first time, a stapling device is available that can be introduced transorally into the gastric area together with a gastroscope. After performing appropriate animal experiments, full-thickness inverted resection of a tumorous section of the gastric wall was done in two patients with early gastric adenocarcinoma. In both patients, the authors were able to resect full-thickness sections of the gastric wall with a diameter of approximately 4 x 4 cm. A gastroscope was used for control of the resected areas in the stomach; one patient required endoscopic hemostasis. The further postoperative course was uneventful in both patients. The method presented herein offers, for the first time, an exclusively transoral, surgical procedure for full-thickness resection of the gastric wall. In addition to early gastric adenocarcinoma with incipient infiltration of the submucosa, possible indications for this procedure include gastrointestinal stromal tumors.