BACKGROUND Left ventricular thrombus (LVT) is a complication of left ventricular dysfunction and myocardial infarction (MI) and is associated with systemic thromboembolism. Two-dimensional transthoracic echocardiography (TTE) is considered the first-line diagnostic tool for detection of LVT. Vitamin K antagonists (VKA) targeting an international normalized ratio (INR) from 2 to 3 are the only approved treatments by the Food and Drug Administration (FDA). New emerging observational data support the use of direct oral anticoagulants (DOACs) as an alternative therapeutic option; however, their safety and efficacy have not been assessed in a good-quality randomized controlled trial. CASE REPORT Here, we present a case of a 43-year-old man diagnosed with human immunodeficiency virus (HIV)-associated dilated cardiomyopathy complicated with an LVT. He was treated with rivaroxaban for 9 consecutive months with no interruption of therapy at any point in time; however, he presented to the emergency department with symptoms of decompensated heart failure. A follow-up TTE demonstrated a significant increase in the size of his LVT. This case questions the efficacy of using factor Xa inhibitor (rivaroxaban) as an alternative option for LVT treatment. CONCLUSIONS This case demonstrates a failure of rivaroxaban in treating LVT in a patient with HIV-associated dilated cardiomyopathy. Good-quality randomized clinical trials or prospective studies are required to establish the efficacy and safety of DOACs for LVT treatment as an alternative to VKA.