Objective: We aimed to determine therapeutic effects of novel oral anticoagulants (NOACs) on cardiac thrombi in acute stroke. Methods: We studied consecutive acute ischemic stroke/TIA patients with non-valvular atrial fibrillation who started to take rivaroxaban or dabigatran and was diagnosed as having cardiac thrombi on transesophageal echocardiography (TEE) within 10 days after the admission between July 2012 and July 2013. All continued to take NOACs without additional antithrombotic agents. Plasma concentrations for rivaroxaban were calibrated based on anti-Xa chromogenic assay for rivaroxaban (Stago®) and thrombin clotting time assay for dabigatran (Hemoclot®) just before (trough) and 4h after medication (peak) at steady state. Results: Eight patients (7 men, 52-83 years old) were studied. Their BW ranged 41.0-88.8 kg, CHADS2 ranged 2-5, and NIHSS ranged 2-18. NOACs were initiated at median 3 days and TEE was performed at median 3 days after admission. As a NOAC, one patient took 15 mg o. d. of rivaroxaban, 5 took 10 mg o.d. of rivaroxaban (officially approved dose in Japan) and the other 2 took 110 mg b.i.d. of dabigatran. For all the patients, the thrombus was identified in the left atrial appendage with median size of 14.7 mm; two of them were hyperechoic, being judged as already-organized. In follow-up TEE examinations median 19 days after admission , 5 thrombi disappeared (rivaroxaban in 3, dabigatran in 2), 1 diminished in size (rivaroxaban), and the other 2, all being initially hyperechoic, did not change (rivaroxaban for both). For 6 patients with absolute/partial dissolution of the thrombi, median peak/trough concentrations of rivaroxaban were 69 (19-255)/10 (range10-20) ng/ml, and those of dabigatran were 100 (40-160)/40 (20-60) ng/ml, median peak/trough aPTT was 42/34.5 s in rivaroxaban users and 45/37 s in dabigatran users, and median peak/trough PT was 20.2/12.9 s and 15.3/13.3 s, respectively. Conclusion: Rivaroxaban and dabigatran have potential to resolve non-organized cardiac thrombi. Monotherapy using NOACs may be enough for early prevention of recurrent stroke in patients with cardioembolic stroke/TIA.