BACKGROUND: Although the management of AF has improved over the years, suboptimal adherence to direct oral anticoagulants (DOACs) is a major health concern. Adherence and long-term persistence to DOACs declines over time resulting in increased risks of stroke, major bleeding and death. The objective of this study was to evaluate the association between adherence to DOACs and composite or bleeding events using marginal structural models (MSM). METHODS: A retrospective study was conducted using the Medicare Advantage Plan from January 2016-December 2020. Atrial fibrillation patients prescribed any DOACs were identified. Adherence was calculated using proportion of days covered (PDC). Patients with PDC ≥0.80 were considered adherent. Composite (stroke, systemic embolism, acute coronary syndrome) and bleeding (major and minor) events were calculated for each of the four time periods. A MSM was conducted to estimate the association between adherence and composite/bleeding events by controlling for time dependent covariates and time dependent exposure affected by the prior exposure. RESULTS: A total of 1969 patients with AF were included in the study. Adherence was suboptimal during all the five time periods, and it was ranging from 39.8% to 53.12%. This study did not find any significant association between adherence to DOACs and composite/bleeding events. The safety and efficacy outcomes were comparable among apixaban, rivaroxaban, and dabigatran. CONCLUSION: This study revealed that adherence declined over time among elderly AF patients. Future studies should explore the association between adherence to DOACs and health outcomes for a longer duration of follow-up using MSM.