The NAVIGATE-ESUS and the RE-SPECT ESUS randomized trials assessed the risk of recurrent ischemic stroke comparing aspirin antiplatelet therapy to 2 NOACs rivaroxaban and dabigatran. Major bleeding events from both trials suggest ineffective and unsafe results from indiscriminate anticoagulant treatment with NOAC rivaroxaban or dabigatran for patients with ESUS, stressing the importance of performing comprehensive diagnostic work-ups in patients to assist in uncovering occult causes of Embolic stroke of underdetermined source.