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PurposeTo evaluate the efficacy and safety of triple antithrombotic therapy (TT) versus dual antiplatelet therapy (DAPT) for prevention of left ventricular thrombus (LVT) following anterior myocardial infarction.MethodsWe conducted a systematic review and meta-analysis of randomized and observational studies comparing TT (DAPT plus anticoagulation) versus DAPT alone. The primary outcome was LVT formation. Secondary outcomes included all-cause mortality, stroke, systemic embolism, composite thromboembolism, bleeding, and net adverse clinical events (NACE). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. The protocol was registered in PROSPERO (CRD420261343867).ResultsSeven studies (2 randomized, 5 observational), including 2,273 patients (949 TT, 1,324 DAPT), were analyzed. TT was not associated with a reduction in LVT (OR 0.56, 95% CI 0.21-1.49; p=0.25; I²=59%). There was no significant difference in all-cause mortality (OR 0.75, 95% CI 0.27-2.06; p=0.58), ischemic cerebrovascular accidents (OR 1.17, 95% CI 0.20-6.79), systemic embolism (OR 0.69, 95% CI 0.27-1.75), or composite thromboembolism (OR 0.96, 95% CI 0.42-2.19). TT was associated with increased major bleeding (OR 2.82, 95% CI 1.40-5.68; p=0.004) and any bleeding (OR 2.58, 95% CI 1.73-3.85; p<0.001). There was no significant difference in NACE (OR 1.15, 95% CI 0.58-2.29).ConclusionIn anterior myocardial infarction, available evidence did not demonstrate a statistically significant reduction in LVT or thromboembolic events with TT compared with DAPT, while bleeding risk was increased. Given moderate heterogeneity, limited randomized evidence, and potential imaging-related under-detection of LVT, these findings do not support routine prophylactic TT and favor individualized risk-benefit assessment.