Background and Aims Flexible endoscopic septum division (FESD) is a rapidly evolving technique for the treatment of Zenker's diverticulum (ZD). The aim was to perform a systematic review and meta-analysis of the literature focusing on FESD for ZD, including an in-depth evaluation of its efficacy, safety, and limitations. Methods A comprehensive literature search was completed to identify papers that examined the efficacy and safety of FESD for ZD. Demographic, clinical, and technical information was retrieved. Main outcomes were extracted, pooled, and analyzed. Heterogeneity among studies was assessed using the I2 statistic. A random effect model was used as the pooling method in cases of high heterogeneity; otherwise the fixed effect model was applied. Meta-regression was also performed. Main outcomes such as rates of success, adverse events, and recurrences were evaluated. Results Twenty studies with a total of 813 patients were selected. The pooled success, adverse events, and recurrence rates were 91% (95% confidence interval CI, 86%–95%; I2  = 69.5%), 11.3% (95% CI, 8%–16%; I2  = 64%), and 11% (95% CI, 8%–15%; I2  = 38.4%), respectively. Substantial heterogeneity across studies was found. However, for success rates, excluding 3 studies reduced heterogeneity to non-significant rates I2  = 25.6%; P  = .154. Adverse event rates decreased with larger samples (coefficient, −0.0123; 95% CI, −0.03 to −0.003; P  = .017), whereas recurrence rates increased (coefficient, 0.006; 95% CI, −0.0010 to 0.0125; P  = .093). Year of publication was negatively associated with success rate, whereas the opposite pattern was found for recurrence rates. Conclusions FESD is a feasible, safe, and effective treatment for symptomatic ZD, with low adverse event and recurrence rates.