Zenker's diverticulum (ZD) is the most common type of esophageal diverticulum. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of endoscopic submucosal tunneling techniques (ESTTs) and flexible endoscopic septotomy (FES) for treating patients with ZD, including subgroup analyses by follow-up duration (<12 months and ≥12 months), diverticulum size (<2.5 cm and ≥2.5 cm), ESTT used (Zenker’s peroral endoscopic myotomy and peroral endoscopic septotomy), and publication format (full text and abstract).

We searched PubMed, EMBASE, and Cochrane Library databases until June 20, 2024. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for continuous and binary outcomes, respectively. Heterogeneity was assessed with the I² statistics.

We included 9 studies (759 patients). Compared with FES, ESTT had a higher probability of clinical success (RR, 1.15; 95% CI, 1.04-1.28). The results were similar in both groups for clinical recurrence (RR, .56; 95% CI, .29-1.07), technical success (RR, .99; 95% CI, .97-1.01), operative time (MD, 7.22 minutes; 95% CI, –.33 to 14.76), hospital stay (MD, .47 days; 95% CI, –1.25 to 2.19), and overall adverse events (RR, 1.19; 95% CI, .44-3.18). Subgroup analyses showed consistent results.

ESTT demonstrated a higher probability of clinical success and showed a trend toward a lower recurrence rate compared with FES; however, both groups had similar technical success, operative time, length of hospital stay, and overall adverse events. These findings underscore ESTT as an effective and safe method for treating patients with ZD.