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Abstract Background and Aims Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta‐analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT. Methods Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all‐cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio. Results Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07–1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36–1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52–0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53–0.96) were also significantly lower in the DOAC group. Conclusion DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance.