Purpose <p>This study preformed to investigate the safety and effectiveness of the Watchman and LAmbre occluders in left atrial appendage closure (LAAC) for the prevention of thrombosis and stroke in patients with atrial fibrillation (AF).</p> Methods <p>A retrospective analysis was conducted on 93 patients with nonvalvular atrial fibrillation (NVAF) who underwent LAAC at Northern Jiangsu People’s Hospital from January 2020 to February 2023. Of these, 48 were implanted with the Watchman occluder and 45 with the LAmbre occluder.</p> Results <p>Differences in LAA opening diameter and left atrial diameter between groups were statistically significant (<i>P</i> &lt; 0.001, <i>P</i> = 0.012). The complete occlusion rate of the LAA in the Watchman group was 45.83% (22/48), compared to 24.44% (11/45) in the LAmbre group, with a significant difference between groups (<i>P</i> = 0.031 &lt; 0.05). Neither group experienced any transient ischemic attacks, cardiac tamponade, or deaths during the perioperative period. Three-month postoperative CTA check-ups showed no displacement or detachment of occluders in either group. The incidence of residual shunt measured by CTA was significantly lower in the Watchman group than in the LAmbre group. The most common occurrence in both groups was a 1–3&#xa0;mm peri-device leak (PDL) at the edge of the occluders. One major PDL (≥ 5&#xa0;mm) occurred in the LAmbre group. Both groups had device-related thrombosis (DRT) on the atrial side of the occluder, all of which were in patients with PDL and disappeared after 3 months of systemic anticoagulation therapy.</p> Conclusion <p>Both the LAmbre and Watchman occluders show high safety and clinical prognosis in LAAC treatment for AF.</p>