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BACKGROUND Left ventricular thrombus (LVT) is a well-defined complication of myocardial infarction and congestive heart failure that has an increased risk of morbidity, mortality, and development of systemic embolism. Vitamin K antagonists, such as warfarin, remain the criterion standard therapy. Although direct oral anticoagulants have been shown to be more effective than warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation, there is insufficient and debatable evidence on their efficacy for the treatment of LVT. CASE REPORT A 62-year-old man with multiple comorbidities and a high risk of thrombosis and bleeding risk had a recurrence of stroke secondary to an increase in LVT size while on apixaban 2.5 mg twice daily for 6 months. It was concluded that the patient experienced treatment failure and therefore was switched to warfarin 5 mg. Upon follow-up, a complete resolution was achieved after 5 months. CONCLUSIONS We report a case of recurrence of ischemic stroke and an increase in the size of LVT during apixaban administration in a patient with severe ischemic cardiomyopathy and advanced chronic kidney disease who successfully achieved a complete resolution when shifted to warfarin. This case report questions the hypothesis on the efficacy of apixaban for patients with high risk of thrombosis and bleeding risk and advanced chronic kidney disease.