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Background: This present study aimed to investigate the impact of left atrial appendage (LAA) isolation on adverse clinical outcomes, with a further stratified analysis by biatrial (BA) and left atrial lesion sets, in patients with atrial fibrillation (AF) undergoing surgical ablation (SA) concurrent with mitral valve (MV) surgery., Methods: We evaluated 875 patients (aged 65.1±12.0 years) who underwent SA of AF concomitant to MV surgery, excluding those with mechanical prostheses requiring lifelong anticoagulation, between 2005 and 2017 in five tertiary cardiac centres in South Korea. Of these, 458 had isolated the LAA, whereas the remainder (n=417) had the LAA preserved. Comparative risk of stroke, mortality and AF recurrence was assessed between the groups, considering death as a competing event. Inverse-probability treatment weighting was used for baseline adjustment., Results: During the median follow-up of 57.4 months (IQR, 32.5-92.4 months), the adjusted risk of long-term stroke was significantly lower in the patients who underwent LAA isolation compared with those who preserved the LAA (subdistribution HR (SHR), 0.28; 95% CI 0.15 to 0.51; p<0.001). However, there were no significant differences in the adjusted risk of mortality (HR, 0.85; 95% CI 0.57 to 1.27; p=0.429) or AF recurrence (SHR, 0.92; 95% CI 0.78 to 1.08; p=0.291) between LAA isolation and preservation. In the subgroup of patients who underwent BA ablation, LAA isolation was associated with a lower long-term risk of stroke and AF recurrence (SHR, 0.77; 95% CI 0.61 to 0.94; p=0.029) compared with LAA preservation., Conclusions: Concomitant LAA isolation during SA of AF in patients undergoing MV surgery was associated with a significantly lower risk of long-term stroke, but no survival benefit was observed., Competing Interests: Competing interests: The authors have nothing to disclose with regard to commercial support for the completion of this study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)