Introduction: Left atrial appendage occlusion with the Watchman device has been shown to be noninferior to oral anticoagulation in preventing strokes in patients with atrial fibrillation. The Watchman FLX device was designed to overcome many of the limitations of the Watchman 2.5. Hypothesis: The Watchman FLX will have better short- and long-term safety and efficacy relative to the Watchman 2.5. Methods: We performed an extensive literature search and systematic review of studies that compared the short- and/or long-term safety and efficacy of the Watchman FLX versus Watchman 2.5. Risk ratio 95% confidence intervals (CI) were measured using the Mantel-Haenszel method for dichotomous variables, where a RR<1.0 favors the FLX group. Results: Seven studies with a total of 2315 patients were included, of which 24.0% (n=555) had the FLX and 76.0% (n=1760) had the 2.5 implanted. There were no statistically significant differences in procedural complications or device-related thrombosis, but significantly less peri-device leak at follow-up, as shown in Figure 1. There were no statistically significant differences in pericardial effusion/tamponade (MD 0.54; 95% CI 0.09-3.25) or device embolization (MD 0.44; 95% CI 0.05-4.14). No statistically significant differences were seen in major bleeding (MD 1.06; 95% CI 0.55-2.05), transient ischemic attack, stroke or systemic embolism (MD 0.31; 95% CI 0.08-1.20) or all-cause mortality (MD 1.65; 95% CI 0.76-3.57) at follow-up. Conclusion: Based on the results of this meta-analysis, the Watchman FLX appears to be as safe as the Watchman 2.5, but with lower rates of peri-device leak.