Background: Data on the safety and efficacy of left atrial appendage occlusion (LAAO) in elderly patients are limited. Objectives: This study aimed to compare the outcomes of LAAO between patients ≥80 and <80 years of age. Methods: We included patients enrolled in randomized trials and nonrandomized registries of the Watchman 2.5 device. The primary efficacy endpoint was a composite of cardiovascular/unknown death, stroke, or systemic embolism at 5 years. Secondary endpoints included cardiovascular/unknown death, stroke, systemic embolism, and major and nonprocedural bleeding. Survival analyses were performed using the Kaplan-Meier, Cox proportional hazards, and competing risk analysis methods. Interaction terms were used to compare the 2 age groups. We also estimated the average treatment effect of the device with the use of inverse probability weighting. Results: We studied 2,258 patients, of whom 570 (25.2%) were ≥80 years old, and 1,688 (74.8%) were <80 years old. Procedural complications at 7 days were similar in both age groups. The primary endpoint occurred in 12.0% in the device group vs 13.8% in the control group (HR: 0.9; 95% CI: 0.6-1.4) among patients <80 years of age and in 25.3% vs 21.7%, respectively (HR: 1.2; 95% CI: 0.7-2.0) among patients ≥80 (interaction P = 0.48). There was no interaction between age and treatment effect for any of the secondary outcomes. The average treatment effects of LAAO (compared with warfarin) were similar in the elderly population (compared with younger patients). Conclusions: Despite the higher event rates, octogenarians derive similar benefits from LAAO as their younger counterparts. Age alone should not preclude LAAO in otherwise suitable candidates.