Background: Patients with ventricular thrombus (VT) require anticoagulation therapy and it remains unknown that whether non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are more effective. Objective: We aimed to compare the effectiveness and safety of NOACs with VKAs on the rate of thrombus resolution and clinical outcomes. Methods: MEDLINE, PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database and Wanfang Database, were searched up to November 22, 2021. The primary outcome was the rate of thrombus resolution, and the secondary outcomes were bleeding, stroke or systemic embolism (SSE), stroke and all-cause death. Odds ratio (OR) and 95% confidential intervals (CI) were used for the pooled results. Results: Eighteen studies with 1755 participants (NOACs, n = 607; VKAs, n = 1148) were included. There were no significant differences in thrombus resolution (OR 0.92, 95% CI 0.68–1.23, p = 0.558), bleeding (OR 0.85, 95% CI 0.54–1.35, p = 0.496), SSE (OR 0.77, 95% CI 0.41–1.43, p = 0.401), stroke (OR 0.65, 95% CI 0.29–1.49, p = 0.312) or all-cause death (OR 1.02, 95% CI 0.63–1.67, p = 0.925) between NOACs and VKAs. Subgroup analyses showed a statistics difference in thrombus resolution between NOACs and VKAs among studies which enrolled patients with or without dabigatran (Yes: OR 0.80, 95% CI 0.59–1.08; No: OR 1.48, 95% CI 1.00–2.19; p = 0.01), while no significances were observed according to baseline characteristics. Conclusions: Our findings showed that NOACs were comparable to VKAs in thrombus resolution as well as clinical outcomes. In studies that enrolled patients without dabigatran, the thrombus resolution seemed to be greater in NOACs group than VKAs group. And in different proportion of baseline left ventricular ejection fraction, history of ischemic cardiomyopathy and combination with antiplatelet, the thrombus resolution among the two groups remained similar.