Background <p>Left Atrial Appendage Occlusion (LAAO) is an alternative therapy for atrial fibrillation (AF) patients at high risk of stroke who have contraindications to long term oral anticoagulation (OAC). However, real-world data specifically regarding the Amplatzer™ Amulet™ device remains limited in Southeast Asian (SEA) populations. This study evaluated the procedural characteristics, safety profiles and 1-year clinical outcomes of the Amulet™ device in the multi-country SEA cohort.</p> Methods <p>This was a multicentre observational study included four centres across three SEA countries (Malaysia, Indonesia and Thailand) from February 2019 to January 2024. The primary outcome was a composite of cardiac mortality and ischemic stroke at 1 year.</p> Results <p>A total of 104 patients were enrolled. The mean age was 67.2 ± 10.1 years old and 67.3% male. The mean CHA₂DS₂-VASc was 4.02 ± 1.45 and mean HAS-BLED score was 3.11 ± 1.17. Majority of the patients (64.4%) had ≥ 2 indications for LAAO implantation. Main indications for LAAO implantation were HAS-BLED score ≥ 3 (55.8%), contraindication for OAC because of renal failure (41.3%) and contraindication for OAC because of bleeding (24.0%). Intracardiac echocardiogram was used in 19.3% of the procedure. The periprocedural complications rate was 2.9%. Device implantation was successful in 98.1%, and 77.9% was successful at first deployment. The 1-year all-cause mortality was 10.6%, with 2.9% cardiac related mortality. Risk of recurrent stroke at 1-year was 1.9% with 1 (1%) major bleeding event. At 12-month, 83.5% of the patients were on single or no antiplatelet therapy.</p> Conclusions <p>Patients from SEA had multiple indications for LAAO. Overall, the dual-seal Amulet™ device demonstrated high procedural success, low complication rates and associated with low rate of AF-related thromboembolic event while using single antiplatelet therapy in most of the patients. (280 words)</p> Graphical Abstract <p></p>