BACKGROUND: Atrial fibrillation (AF) is a major risk factor for the development of stroke and silent cerebral infarct (SCI). Additionally, AF is independently associated with neurological disorders, including cognitive impairment and dementia. Although oral anticoagulants (OACs) are used to reduce the risk of development of stroke and SCI in patients with AF, it is unclear whether OACs reduce the risk of dementia. OBJECTIVE: This study aimed to investigate the association between OAC use and dementia in relatively young patients with AF. Moreover, the impact of medication adherence on the association between OAC use and the risk of dementia was examined. PATIENTS AND METHODS: This retrospective cohort study was conducted using a large claims database-Japan Medical Data Center, Inc. (JMDC)-from which newly diagnosed patients with AF younger than 75 years of age were identified. We analyzed medication adherence using the medication possession ratio (MPR). The dementia risk was compared between the OAC and non-OAC groups using Cox proportional hazards regression analysis and the Kaplan-Meier method after propensity score matching. Similarly, the MPR-classified and non-OAC groups were also compared. RESULTS: OAC administration was not associated with the risk of dementia in the entire cohort (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40-1.08; p = 0.098); however, OAC administration in patients with an MPR ≥90% was significantly associated with a lower risk of dementia (HR 0.45, 95% CI 0.25-0.81; p = 0.008). Meanwhile, direct OAC (DOAC) and warfarin (WF) administration was not associated with the risk of dementia regardless of MPR. Kaplan-Meier analysis revealed a significant difference in the incidence of dementia between the MPR ≥ 90% OAC and non-OAC groups (log-rank test: p = 0.006). However, no difference was observed in the incidence of dementia between the MPR ≥ 90% WF and non-OAC groups, or between the MPR ≥ 90% DOAC and non-OAC groups. CONCLUSIONS: OAC administration was not associated with the risk of dementia in relatively young patients with AF; however, when limited to patients with an MPR ≥ 90%, OAC administration reduced the risk of dementia. Our results suggest that the association between OAC use and dementia should be evaluated while considering medication adherence.