Current guidelines recommend vitamin K antagonists (VKAs) for left ventricular thrombus (LVT) resolution. Direct oral anticoagulants (DOACs) are increasingly evaluated as alternatives to the standard of care in anticoagulation. We performed a systematic review and meta-analysis to assess the use of DOACs vs VKAs for LVT treatment. The occurrence of LVT resolution, systemic embolism (SE) or stroke, and bleeding events were compared during follow-up using random-effects analysis. The 5 included studies were all observational (a total of 828 patients). Of these, 284 patients (34%) were treated with DOACs, and 544 (66%) treated with VKAs. Thrombus resolution was similar for both methods (pooled odds ratio [OR], 0.91; 95% CI, 0.47-1.75; I2 = 63%; P = .78). The incidence of SE or stroke was also similar (pooled OR, 1.59; 95% CI, 0.85-2.97; I2 = 0%; P = .14). Clinically relevant bleeding incidence was similar for both groups (pooled OR, 0.66; 95% CI, 0.31-1.40; I2 = 0%; P = .28), although all bleeding events were less frequent in the DOAC group (pooled OR, 0.49; 95% CI, 0.26-0.90; I2 = 0%; P = .02). Our systematic review and meta-analysis suggests DOACs were as effective as VKAs for LVT resolution, with a similar risk of systemic embolism/stroke and clinically relevant bleeding. These results, obtained from observational studies, are not definitive and hence randomized controlled trials are needed. Nevertheless, our analysis identifies key experimental features required in future studies.