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Introduction: Due to the aging population, the number of elderly patients with atrial fibrillation and contraindications for anticoagulation due to bleeding complications is growing. After the epicardial ligation of the left atrial appendage (LAA), anticoagulation can be omitted. We present the single-center procedure data and long-term data of octogenarians being treated with LARIAT^®. Method: Out of 145 patients eligible for the epicardial ligation of the LAA, 45 were older than 80 y and included in this analysis. After successful ligation, patients were screened at 6 weeks of follow-up (FUP), at 12 weeks and after 12 months for transesophageal echocardiography (TOE) and clinical events. During long-term FUP, TOE sessions and clinical events for embolic events and death were documented. Results: The procedure was successful in 93% of patients, with a mean CHA₂DS₂VASC score of 4.6 and HASBLED score of 3.7 and a mean age of 82 y. One major complication occurred, with the laceration of the LAA and surgical closure of the LAA with an Atriclip. The 6-week FUP data were available in 39 patients, with the detection of four leaks (1–3 mm, median 2 mm) and three thrombi; one thrombus occurred at the site of a leak. The 12-week FUP (in 26 patients) showed that three leaks were closed, one leak persisted and one new thrombus developed at the site of the leak. All thrombi were resolved. The 12-month FUP showed the persistent resolution of three thrombi; one thrombus recurred after the withdrawal of the anticoagulant, and no new gap or thrombus could be detected. The long-term FUP (mean 38 months) was documented in 30 patients, with no new gaps and no new thrombi; one patient suffered from a stroke, with a good long-term result of LAA closure in TOE (stroke rate 1%/y, absolute risk reduction of 4.4% to a stroke rate of 5.4% related to the score, relative CHA₂DS₂VASC risk reduction of 88%). Eleven patients died: four in the first year of ligation and seven during long-term FUP. Conclusions: The epicardial ligation of the LAA for stroke prevention in octogenarians is highly safe and effective. Early TOE FUP is crucial for the detection of thrombi and establishing an optimal anticoagulation regime. No late development of thrombi or gaps can be observed at up to 5 years. Full article