Background/AimsAlthough several groups have demonstrated the usefulness of natural orifice transluminal endoscopic surgery (NOTES), there is still concern about frequent serious adverse events. We performed this study to determine the technical feasibility and safety of pure NOTES with a transgastric approach in a porcine model from the endoscopist's point of view.MethodsDiagnostic peritoneoscopy, liver biopsy, salpingo-oophorectomy, and Fallopian tube ligation with a transgastric approach using a two-channel therapeutic endoscope were performed in 10 healthy female minipigs. These procedures were performed in two acute models and eight survival models in consecutive order.ResultsThe technical success rate was 100% for peritoneoscopy (10/10), liver biopsy (5/5), salpingo-oophorectomy (10/10), and Fallopian tube ligation (10/10). Eight cases of adverse events occurred, including one case of splenic injury, one case of bleeding after liver biopsy, two cases of small bowel adhesion after salpingo-oophorectomy, two cases of hematoma at the salphingo-oophorectomy site, and two cases of partial dehiscence at the gastric closure site. The gastric puncture site was closed with seven to eight hemoclips in four cases and two hemoclips and an endoloop in four cases.ConclusionsThe use of pure NOTES for peritoneoscopy, liver biopsy, salpingo-oophorectomy, and Fallopian tube ligation may be technically feasible, but considerable adverse events can occur during or after the procedure. Further studies utilizing specialized techniques overcome several limitations of pure NOTES are therefore necessary.