Background and AimsObesity is a global health problem, and less-invasive treatments are warranted. We developed a novel endoscopic intervention named peroral endoscopic myo-neurotomy (POEM-N) that is performed at the greater curvature of the gastric antrum as a bariatric/metabolic procedure and assessed its feasibility using porcine models. MethodsSix live pigs were divided into three groups of two: POEM-N with high-fat diet (HFD) (POEM-N group); sham procedure with HFD (HF-control group); and sham procedure with normal diet (N-control group). All pigs were fed the diets for 2 weeks, underwent POEM-N or sham procedure, and were followed up for 2 weeks after the procedure. The primary outcome was the safety and feasibility of POEM-N. Adverse events and the histology of the area after POEM-N were evaluated to assess the procedure’s safety and feasibility. The secondary outcomes were the changes in body weight and glycolipid levels. ResultsThere was no severe worsening of vital signs during or after the POEM-N procedure. All pigs were well and food intake was good, with no delayed adverse events. Excessive storage of dietary residue, deformity of the gastric antrum and fold concentration were observed after POEM-N, as expected. Histological examination showed hypertrophic regeneration of Auerbach’s plexus, which regulates gastric peristalsis, in both POEM-N pigs. After the procedure, HFD-induced weight gain in POEM-N pigs slowed down, and the increase in serum and liver cholesterol level was suppressed. ConclusionsWe applied POEM-N as a bariatric/metabolic procedure and showed its safety and feasibility using porcine models.