BACKGROUND Left atrial appendage (LAA) triggers play a crucial role in atrial fibrillation (AF) and can be effectively treated through complete LAA isolation. However, the current literature presents conflicting findings regarding the risks of LAA thrombus and thromboembolism after this procedure. Some researchers argue that the loss of contractility may lead to blood flow stasis, thereby increasing the risk of thrombus formation and thromboembolism in AF patients. In contrast, other clinical studies indicate that LAA isolation does not raise the risk of thrombus formation. OBJECTIVES The authors sought to perform a meta-analysis of controlled studies assessing the risk of LAA thrombus and thromboembolism in patients with AF undergoing isolation of the LAA. METHODS A systematic review of PubMed, Cochrane, and Embase was conducted for clinical studies published up to December 6, 2024, assessing the relationship between LAA isolation and thrombus formation. The primary endpoint was LAA thrombus formation or embolic events. The association between LAA isolation and thrombus formation was estimated using random-effects modeling. The risk ratio (RR) with 95% confidence intervals (CIs) was calculated using the DerSimonian and Laird method. RESULTS The study included five clinical studies with a total of 3,976 patients, of whom 851underwent LAA isolation. The analysis revealed that LAA isolation was associated with a significantly increased risk of LAA thrombus formation or transient ischemic attack (TIA)/stroke compared to those who did not undergo LAA isolation (RR 6.05, 95% CI 2.85–12.85; P < 0.0001; I 2 = 49%). The increased risk was particularly evident in prospective studies (RR 8.75, 95% CI 3.73–20.53; P < 0.0001; I 2 = 0%) and in studies with a follow-up period longer than two years (RR 7.39, 95% CI 4.4–12.41; P < 0.0001; I 2 = 15%). When focusing on well anticoagulated subjects, the major conclusion remained unchanged (RR 18.80, 95% CI 5.37–65.82; P < 0.0001; I 2 = 0%). Following LAA isolation, there was a significant decline in LAA flow velocity (SMD: -0.70; 95% CI: -1.33—0.07; p = 0.03; I 2 = 91%). In contrast, a significant increase in the degree of smoke in the LAA was observed (SMD: 1.33; 95% CI: 0.23–2.43; p = 0.02; I 2 = 95%) compared to preoperative function. CONCLUDE LAA isolation was associated with a significantly increased risk of LAA thrombus formation or thromboembolic events compared to those who did not undergo LAA isolation, even with ongoing anticoagulant therapy. More randomized trials are needed to explore safer ablation strategies that minimize the risk of thromboembolism after LAA isolation.