Abstract Aims Data on safety outcomes of left atrial appendage occlusion (LAAO) in elderly patients are limited. This study aimed to compare the outcomes of LAAO between octogenarians (age 80–89) and nonagenarians (age ≥90) vs. younger patients (age ≤79). Methods and results We conducted a retrospective cohort study using the National Inpatient Sample database to identify patients hospitalized for LAAO from 2016 to 2020 and to compare in-hospital safety outcomes in octogenarians and nonagenarians vs. younger patients. The primary outcome was a composite of in-hospital all-cause mortality or stroke. Secondary outcomes included procedural complications, length of stay (LOS), and total costs. Outcomes were determined using logistic regression models. Among 84 140 patients hospitalized for LAAO, 32.9% were octogenarians, 2.8% were nonagenarians, and 64.3% were ≤79 years of age. Over the study period, the volume of LAAO increased in all age groups (all Ptrend < 0.01). After adjustment for clinical and demographic factors, octogenarians and nonagenarians had similar odds of in-hospital all-cause mortality or stroke [adjusted odds ratio (aOR) 1.41, 95% confidence interval (CI) 0.93–2.13 for octogenarians; aOR 1.69, 95% CI 0.67–3.92 for nonagenarians], cardiac tamponade, acute kidney injury, major bleeding, and blood transfusion, in addition to similar LOS and total costs compared with younger patients (all P > 0.05). However, octogenarians and nonagenarians had higher odds of vascular complications compared with younger patients (aOR 1.47, 95% CI 1.08–1.99 for octogenarians; aOR 1.60, 95% CI 1.18–2.97 for nonagenarians). Conclusion Octogenarians and nonagenarians undergoing LAAO have a similar safety profile compared with clinically similar younger patients except for higher odds of vascular complications.