Background and Aims: The novel use of peroral endoscopic myotomy (POEM) in the treatment of Zenker's diverticulum (ZD) was recently described in case reports. The aim of this study is to report a multicenter experience with the POEM technique in the management of ZD. Methods: This is a multicenter international retrospective study involving 10 centers. The Zenker's POEM technique was performed using principles of submucosal endoscopy. Results: Seventy-five patients (73.3 ± 1.2 years, 33 women) were included with a mean Charleson comorbidity index of 4 ±.2. The mean size of ZD was 31.3 ± 1.6 mm (range, 10-89). The overall technical success rate was 97.3% (73/75). There were 2 technical failures because of the inability to locate the septum and failed tunnel creation. Adverse events occurred in 6.7% (5/75): 1 bleed (mild) conservatively managed and 4 perforations (1 severe, 3 moderate). The mean procedure time was 52.4 ± 2.9 minutes, and mean length of hospital stay was 1.8 ±.2 days. Clinical success was achieved in 92% (69/75) with a decrease in mean dysphagia score from 1.96 to.25 (P <.0001). The median length of follow-up was 291.5 days (interquartile range, 103.5-436). At the 12-month follow-up, 1 patient reported symptom recurrence. Conclusions: Endoscopic management of ZD using the POEM technique is novel and feasible with promising efficacy and safety results. Long-term follow-up is needed to ensure durability of response. In addition, comparative studies with other treatment modalities are warranted.