Atrial fibrillation (AF) is associated with an increased risk of dementia. Emerging evidence suggests AF suppression is associated with reduced risk of dementia, but the optimal strategy to achieve this is unknown. We sought to compare the risk of dementia in patients with AF who underwent catheter ablation (CA) versus anti-arrhythmic drug (AAD) treatment. METHODS AND RESULTS: Using the 2000 to 2021 Optum Clinformatics database, patients with AF who underwent CA versus AAD treatment (≥1 prescription fill for ≥2 different AADs) were identified and propensity score matched overall and within sex subgroups. A cause-specific hazard model was performed to assess dementia overall and in sex-specific subgroups. After matching, there were 19,088 patients per group. CA was associated with a 41% lower risk of dementia compared with AAD alone (1.9% vs 3.3%; hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.52-0.67, log-rank P < .0001). When examined by sex, dementia risk reduction associated with CA versus AAD use alone was observed among both males (HR 0.55, 95% CI 0.46-0.66) and females (HR 0.60, 95% CI 0.50-0.72). Though not studied as a primary outcome, patients treated with CA were also observed to have 49% lower associated risk of mortality compared with AAD only (HR 0.51 95% CI 0.46-0.55, P < .0001). CONCLUSIONS: Among patients treated for AF, CA was associated with significantly lower risk of dementia and death compared with AADs only. These reductions in risk associated with CA versus AAD were seen in both males and females.