Traditional management of Zenker’s diverticulum (ZD) has relied on rigid endoscopic septotomy or open surgical approaches, both associated with higher procedural burden and complication rates, particularly in elderly or comorbid patients. Over the past two decades, flexible endoscopy has become an important minimally invasive alternative, offering flexible endoscopic septotomy (FES) as a valid therapeutic option with shorter recovery time and fewer complications. However, despite its advantages, FES remains limited by incomplete myotomy and technically challenging exposure in certain anatomies, which can lead to recurrence. Zenker’s peroral endoscopic myotomy (Z-POEM) has emerged over the past decade as a minimally invasive alternative that enables a controlled submucosal tunneling approach and complete septal division. Although Z-POEM adoption has increased internationally, high-volume single-center analyses with consecutive, prospectively collected cases remain limited.This study aimed to evaluate the safety profile, efficacy and degree of procedural standardization achieved throughout our experience with the first 100 consecutive Z-POEM procedures at a tertiary referral center. 

We conducted a retrospective analysis of all consecutive patients undergoing Z-POEM between October 2020 and November 2025. Demographic characteristics, symptom duration, and diverticulum size were recorded. Diverticulum dimensions were extracted both from endoscopy (EGDS) and radiographic imaging (Rx). Procedural data included type of knife, use of guidewire, myotomy length, number of clips for mucosal closure, procedure duration, and in-hospital course.Clinical outcomes were assessed through symptom scores (Kothari), adverse events (AEs) graded according to ASGE lexicon, technical success, clinical success, and need for retreatment. Follow-up was performed through scheduled visits, telephone interviews, and additional endoscopy when indicated.

A total of 100 patients (61% male; mean age 70.5±10.4 years; BMI 24.6±3.1 kg/m²) were included. Pretreatment symptoms persisted for a mean of 29±39 months, and 95% of patients were treatment-naïve, reflecting the role of our center as a primary referral site. Mean diverticulum size measured 14.7±7.9 mm on EGDS and 24.9±13.1 mm on Rx.All procedures were performed by three expert endoscopists using low-flow CO₂ insufflation and the TT-knife J in 98% of cases, supporting high procedural standardization. Guidewire placement was required in only 3% of cases, predominantly in anatomically challenging presentations. The mean myotomy length was 19.7±7.2 mm, and closure was achieved with an average of 3.4±0.8 clips.Technical success reached 98%, two procedures were aborted due to the inability to obtain sufficient exposure of the diverticular septum during the tunneling. Procedures were efficient, with a mean duration of 17.9±7.3 minutes and a mean hospitalization of 2.2±1.5 days.During the index procedure, two mucosal perforations occurred but were immediately identified and managed endoscopically without clinical sequelae. No AEs occurred or conversions to alternative techniques were reported.At final follow-up (mean 22.2±12.6 months; 23% lost), 88% of patients maintained sustained symptom relief (Kothari ≤4). The mean Kothari score showed a significant improvement, decreasing from 3.12 pre-procedure to 1.22 at the final follow-up, corresponding to a mean difference of 1.90 (95% CI 1.36–2.44; p < 0.05). Retreatment was required in eight patients (8%): repeat Z-POEM in 3% and FES in 5%. All reinterventions were completed endoscopically, without further complications, underscoring the manageable nature of recurrent symptoms.

Our experience demonstrates that Z-POEM is a highly effective, safe, and reproducible technique for the management of Zenker’s diverticulum. Technical success was consistently high across operators, while procedure time, resource utilization, and length of stay remained low, reflecting progressive standardization within the center. The absence of severe AEs or surgical conversions, and excellent long-term clinical response reinforce the role of Z-POEM as a first-line endoscopic therapy for ZD.