The off-label use of direct oral anticoagulants (DOACs) for the treatment of left ventricular thrombi has grown over the past several years given the ease of administration, absence of a requirement for international normalized ratio (INR) monitoring, and freedom from dietary restrictions; however, the evidence for their safety and efficacy is contradictory. We systematically searched PubMed and Google Scholar from January 1, 2009, to April 25, 2020, for studies of DOACs for treatment of left ventricular thrombi. Fifty-three articles (of 1,168 patients) met our inclusion criteria. We found that the studies have reached conflicting results; based on our findings, their routine use for the treatment of left ventricular thrombi cannot be recommended. Adequately powered randomized controlled trials are needed to determine the safest and most effective treatment for left ventricular thrombi.