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Abstract Background Left ventricular thrombus (LVT) is not uncommon and pose a risk of systemic embolism, which can be mitigated by adequate anticoagulation. Direct oral anticoagulants (DOACs) are increasingly being used as alternatives to warfarin for anticoagulation, but their efficacy and safety profile has been debated. We aim to compare the therapeutic efficacy and safety of DOACs versus warfarin for the treatment of LVT. Methodology We systematically searched PubMed/Medline, Google Scholar, Cochrane library, and LILCAS databases from inception to 14th August 2020 to identify relevant studies comparing warfarin and DOACs for LVT treatment and used the pooled data extracted from retrieved studies to perform a meta-analysis. Results We report pooled data on 1955 patients from 8 studies, with a mean age of 61 years and 59.7 years in warfarin and DOACs group, respectively. The pooled odds ratio for thrombus resolution was 1.11 (95% CI 0.51–2.39) on comparing warfarin to DOAC, but it did not reach a statistical significance (p = 0.76). The pooled risk ratio (RR) of stroke or systemic embolization and bleeding in patients treated with warfarin vs DOACs was 1.04 (95% CI 0.64–1.68; p = 0.85), and 1.15 (95% CI 0.62–2.13; p = 0.57), respectively; with an overall RR of 1.09 (95% CI 0.70–1.70; p = 0.48) for mortality. Conclusions DOACs appears to be non-inferior or at least as effective as warfarin in the treatment of left ventricular thrombus without any statistical difference in stroke or bleeding complications.