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Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying, without the presence of a stenosis. For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis. Studies with EndoFLIP, a device that assesses pyloric distensibility, increased the knowledge about pylorospasm. Based on this data, several pyloric-targeted therapies were developed to treat refractory gastroparesis: Surgical pyloroplasty and endoscopic approach, such as pyloric injection of botulinum and pyloric stenting. Notwithstanding, the success of most of these techniques is still not complete. In 2013, the first human gastric per-oral endoscopic myotomy (GPOEM) was performed. It was inspired by the POEM technique, with a similar dissection method, that allows pyloromyotomy. Therapeutical results of GPOEM are similar to surgical approach in term of clinical success, adverse events and post-surgical pain. In the last 8 years GPOEM has gained the attention of the scientific community, as a minimally invasive technique with high rate of clinical success, quickly prevailing as a promising therapy for gastroparesis. Not surprisingly, in referral centers, its technical success rate is 100%. One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.