Background Data on left atrial/left atrial appendage (LA/LAA) thrombus resolution after non–vitamin K antagonist (VKA) oral anticoagulant treatment are scarce. The primary objective of X-TRA was to explore the use of rivaroxaban for the resolution of LA/LAA thrombi in patients with nonvalvular atrial fibrillation (AF) or atrial flutter, with the CLOT-AF registry providing retrospective data after standard-of-care therapy in this setting. Methods X-TRA was a prospective, single-arm, open-label, multicenter study that investigated rivaroxaban treatment for 6 weeks for LA/LAA thrombus resolution in patients with nonvalvular AF or atrial flutter and LA/LAA thrombus confirmed at baseline on a transesophageal echocardiogram (TEE). CLOT-AF retrospectively collected thrombus-related patient outcome data after standard-of-care anticoagulant treatment for 3 to 12 weeks in patients with nonvalvular AF or atrial flutter who had LA/LAA thrombi on TEE recorded in their medical file. Results In X-TRA, patients were predominantly (95.0%) from Eastern European countries. The adjudicated thrombus resolution rate was 41.5% (22/53 modified intention-to-treat [mITT] patients, 95% CI 28.1%-55.9%) based on central TEE assessments. Resolved or reduced thrombus was evident in 60.4% (32/53 mITT patients, 95% CI 46.0%-73.6%) of patients. In CLOT-AF, the reported thrombus resolution rate was 62.5% (60/96 mITT patients, 95% CI 52.0%-72.2%) and appeared better in Western European countries (34/50; 68.0%) than in Eastern European countries (26/46; 56.5%). Conclusion X-TRA is the first prospective, multicenter study examining LA/LAA thrombus resolution with a non-VKA oral anticoagulant in VKA-naïve patients or in patients with suboptimal VKA therapy. Rivaroxaban could be a potential option for the treatment of LA/LAA thrombi. Atrial fibrillation (AF) predisposes patients to the development of atrial thrombi, most often in the left atrial (LA) appendage (LAA). Left atrial appendage thrombi are the dominant source of embolism (>90%) in patients with nonvalvular AF, and  and LA/LAA thrombi are identified in ~10% of patients with AF.3 The use of a transesophageal echocardiogram (TEE) is an established standard for detecting the presence of LA/LAA thrombi.,  and  If an LA/LAA thrombus is detected on a TEE, current guidelines and  recommend vitamin K antagonist (VKA) treatment with a therapeutic international normalized ratio (INR) of 2.0 to 3.0 for at least 3 weeks and a follow-up TEE to ensure thrombus resolution prior to interventions such as cardioversion. However, reported thrombus resolution rates with VKAs vary between approximately 50% and 90% after a median of 4 weeks’ treatment., , , ,  and  Reasons for this wide range of resolution rates include differences in patient populations (eg, with or without the inclusion of valvular AF14; first diagnosed or persistent AF) and anticoagulation strategies/treatment durations, or the use of imaging strategies evaluated in relatively small observational studies., , , ,  and  Data on LA/LAA thrombus resolution after non-VKA oral anticoagulant (NOAC)17 treatment are scarce and largely comprise case reports, which generally indicate favorable outcomes., , ,  and  The primary objective of the prospective X-TRA study was to explore the use of the NOAC rivaroxaban for the resolution of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter who had a TEE-confirmed LA/LAA thrombus. The objective of the CLOT-AF registry was to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter who had TEE-documented LA/LAA thrombi.