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Background: Antithrombotic treatment (ATT) post-left atrial appendage occlusion (LAAO) remains controversial. Furthermore, most of the patients undergoing LAAO are at a very high bleeding risk., Aims: This study aimed to compare a simplified versus conventional ATT after LAAO in very high bleeding risk patients., Methods: This is a multicentre, retrospective study including very high bleeding risk patients, according to the Bleeding Academic Research Consortium (BARC) definition, who underwent LAAO. These included patients at >4% risk of BARC 3 to 5 bleeding or >1% risk of intracranial bleeding after the procedure. Two groups were established based on the discharge ATT. The simplified group included single antiplatelet treatment or no treatment, and the conventional group comprised dual antiplatelet treatment or anticoagulation (combined or not with antiplatelet therapy)., Results: A total of 1,135 patients were included. The mean CHA 2 DS 2 -VASc and HAS-BLED scores were 4.5±1.5 and 3.7±1.0, respectively. There were no differences in the composite endpoint (death, stroke, transient ischaemic attack, device-related thrombus or major bleeding) between the 2 groups (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.59-1.11; p=0.188). Although the rate of major bleeding during the first year was numerically lower in the simplified group, it did not reach statistical significance (HR 0.67, 95% CI: 0.41-1.10; p=0.104). Nonetheless, patients with previous major bleeding presented a significantly lower rate of major bleeding when using the simplified treatment (HR 0.61, 95% CI: 0.36-0.99; p=0.049)., Conclusions: In patients with very high bleeding risk, a simplified ATT after LAAO seems to be as effective as conventional protocols. Furthermore, patients with a history of major bleeding experienced a lower risk of major bleeding with the simplified ATT.