Background We aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event. Methods and Results This was a retrospective cohort study of consecutive patients with preceding established indications for long‐term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management‐relevant high‐risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence‐based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70–84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1–12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1–3) days. TTE identified 26 of 191 (14%) patients with 35 management‐relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management‐relevant pathologies. Most management‐relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management‐relevant high‐risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], C‐reactive protein, d ‐dimer, and troponin levels). Conclusions In patients with established indications for long‐term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management‐relevant high‐risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.