Introduction: Left atrial appendage (LAA) thrombus in atrial tachyarrhythmias is one of the principal causes of stroke. Prevalence and strategies to thrombus resolution has recently been described in the era of the direct oral anticoagulants (DOAC). The aim of the study was to determine the prevalence and strategies to resolve previous LAA thrombus during regular oral antithrombotic therapy in preparation to perform atrial fibrillation (AF) ablation and/or LAA closure. Methods: Between January 2011 and December 2020 we prospectively followed 23 patients (5.39%) that showed LAA thrombus formation. Persistent AF occurred in 13 (56.52%), median age 72.39 years, 15 (65.22%) females, median CHA2DS2VASC of 4.13, HASBLED of 2.28, 17 (73.91%) with hypertension, (52.17%) with coronary disease, 9 (39.13%) had priors’ thromboembolic events, 7 (30.43%) with heart failure and Diabetes. Diagnosis was by transesophageal echocardiogram (TEE) in 20 (86.96%) and the rest by computed angiotomography. Rivaroxaban was used in 11 (47.83%), Dabigatran in 6 (26.09%), 5 (21.74%) with therapeutic range Warfarin and 1 (4.34%) with Apixaban. Main strategy of treatment was to change mechanism of action of antithrombotic medication in association to an antiplatelet drug, Clopidogrel 75mg a day, and perform a TEE at 90 days after. Results: Complete resolution of the LAA thrombus was achieved in 18 (78.26%) patients in first medical therapeutic change. Of the remaining a second approach with medical therapy adjustment with off-label dose prescription associated with Clopidogrel showed complete resolution in 3 (13.04%) totalizing a success rate of 91.30% for all patients (p value of 0.001 for treatment success). The failure of the antithrombotic plus antiplatelet therapy occurred in 2 (8.7%) patients, one with LAA sludge and other with a huge thrombus in all LAA and part of left atrium. Conclusion: Modification of the mechanism of action of direct oral anticoagulants in association with Clopidogrel demonstrates to be successful in a large number of patients with previous resistant left atrial thrombus with and secure since the low adverse event rates.