Background and aim <p>Atrial fibrillation (AF) is a substantial public health disorder associated with heightened morbidity and mortality. Pulmonary vein isolation (PVI) has limited efficacy in persistent AF (PAF), indicating additional strategies such as left atrial appendage electrical isolation (LAAEI). This study evaluates the efficacy and safety of LAAEI in managing PAF.</p> Methods <p>An extensive search of the literature was carried out on PubMed, Scopus, Web of Science, and Cochrane Library. We included all the eligible studies comparing LAAEI plus PVI to PVI alone in managing PAF. Our primary endpoint was the incidence of recurrent atrial arrhythmia. Dichotomous data were pooled as risk ratios (RRs) with 95% confidence intervals (CIs).</p> Results <p>Twelve studies involving 3,425 patients were included in our meta-analysis. LAAEI significantly reduced the incidence of recurrent atrial arrhythmia (RR = 0.57, 95% CI: [0.54 to 0.75], <i>P</i> = 0.001). Furthermore, the subgroup analysis focusing on the utilized anatomical approach showed that the ostial approach favored the LAAEI compared to the control group in reducing the incidence of recurrent atrial arrhythmias, while the linear approach did not favor either of the two groups. The radiofrequency strategy favored the LAAEI group rather than the control group, while the cryoballoon ablation and the LARIAT device did not prefer either of the two groups.</p> Conclusion <p>LAAEI plus PVI is a promising strategy when compared to PVI alone to reduce the incidence of recurrent atrial arrhythmia in patients with PAF.</p>