Background: Standard treatments of Zenker diverticulum are endoscopic stapled diverticulotomy and crycopharingeal myotomy associated or not with either transcervical diverticulectomy or diverticulopexis. Endoscopic flexible diverticulotomy is a mini-invasive alternative. Aim: To evaluate the immediate results and the clinical efficacy at 1 months follow-up of flexible endoscopic myotomy. Methods: A total of 35 patients (74% males; mean age 67 ± 12 years) with Zenker diverticulum (median length 4 cm; range 2-8) were treated in a 5 years period. The endoscopic device used to expose the diverticular septum was the oblique-end plastic hood (MH589, Olympus; Japan) in 26 patients and the flexible double duckbill diverticuloscope (Wilson-Cook, USA) in 9 patients. Myotomy was performed by needle-knife with endocut current (200 ICC, ERBE). Severity of dysphagia for solids and liquids, regurgitation, chronic cough and nocturnal symptoms were graded according to frequency (0, none; 1, weekly; 2 daily) before the procedure and after 1 month. Results: Zenker diverticula had a median depth of 4 cm: 3 (9%) were <3 cm; 23 (66%) were 3-4 cm, and 9 (26%) were >4 cm. Dysphagia and regurgitation were the most common symptoms and were both reported by 94% of patients. Cough, either during meals and/or postprandial was present in 80% patients and nocturnal symptoms in 77%. Myotomy was performed in a single endoscopic session in 94% of patients and in two sessions in 6%. Minor bleeding during the cut was observed in 3 (9%) cases but was easily controlled by electrocoagulation, epinephrine injection or endoclips. Complications occurred in 4 (10%) cases: in two patients a perforation was observed during the procedure and was closed with endoclips, and in two cases subcutaneous emphysema and pneumo-mediastinum were noted 24 hrs after endoscopy. All patients were treated conservatively and discharged after one week. Hospital stay ranged from 2 to 8 days (median 4 days). Dysphagia for solids, regurgitation and chronic cough improved significantly after treatment. All symptoms disappeared in 8 (23%) patients. Four (11%) patients required retreatment and 4 (11%) eventually underwent surgical diverticulectomy. Conclusions: Flexible endoscopic cricopharyngeal myotomy is feasible both for large and small Zenker diverticula and achieves a significant clinical improvement. Extension of the cut of the septum in case of partial clinical response may be successful in a proportion of patients.