In this 8 min video, Ken Butcher provides an overview of ongoing research efforts to treat embolic stroke of undetermined source (ESUS) with non-vitamin K antagonists (NOAC). ESUS refers to a type of stroke with non-lacunar pattern with unclear etiology even after a complete workup. ESUS patients have an elevated risk of stroke recurrence compared to non-ESUS type strokes. The rationale for testing NOACs in ESUS patients is based on the hypothesis that many events are likely related to thromboembolic mechanisms or subclinical atrial fibrillation. The WARSS trial showed that warfarin (INR 1.4-2.8) was not inferior to ASA in preventing recurrent events after non-cardioembolic stroke. The recent NAVIGATE ESUS trial comparing rivaroxaban vs ASA was terminated early due to the lack of a significant difference in the risk of recurrent stroke and an excess of major bleeding in the rivaroxaban arm. Another ongoing trial is RE-SPECT ESUS, comparing dabigatran with ASA in patients with ESUS. Results will be presented at the World Stroke Congress in October 2018. Positive results of this trial may influence current practice and guidelines.