BACKGROUND : Mid-esophageal and epiphrenic diverticula (MED) can be associated with esophageal motility disorders. Per-oral endoscopic myotomy (POEM) is an established treatment for esophageal motility disorders that has also been introduced for the treatment of MED. METHODS : Data were prospectively collected from patients with MED treated with POEM at our institution. When esophageal motility disorders were present, myotomy was performed extending the myotomy to the lower esophageal sphincter (LES) to treat the motility dysfunction associated with the diverticulum. In the absence of esophageal motility disorder, POEM was performed without including the LES in the myotomy to achieve diverticulotomy. RESULTS : Four patients were treated with POEM for MED between April 2017 and March 2018. The patients suffered from distal esophageal spasm, jackhammer esophagus or esophago-gastric junction outflow obstruction. One patient had no esophageal motility disorder. Diverticulum size was 3 cm in one case and 6 cm in the others. Preoperative Eckardt scores ranged from 6 to 8. No life-threatening complications were reported. Intraoperative pneumoperitoneum was described in two cases and one patient experienced aspiration pneumonia. The patients with motility disorders were asymptomatic at 6-8 months follow-up. The patient without documented underlying esophageal motility disorder had an Eckardt score of 3 at 9-months follow-up. Two cases of gastro-esophageal reflux were successfully managed with proton pump inhibitors. CONCLUSIONS : In the case of MED and esophageal motility disorder, POEM permitted treatment of the underlying cause of the diverticulum, achieving favorable early clinical outcomes. In the absence of motility disorder, POEM was feasible with promising early outcomes, and could be a valid alternative to surgical diverticulectomy in selected patients.