Purpose: Atrial fibrillation (AF) is associated with increased risk of thromboembolisnn, and is also a predisposing factor to dementia. Our investigation was a retrospective observational study to evaluate whether the usage of angiotensin-converting-enzyme inhibitor (ACE) or angiotensin II receptor blocker (ARB) could reduce the incidence of dementia in patients with AF. Methods: A total of 5221 patients over 20 years of age who had a history of AF as noted in ambulatory and inpatient claims data were enrolled from the National Health Insurance Research Database of Taiwan in 1997 and 1998. Patients with ACEI or ARB were designated as group 1 (4343 patients), and patients without ACEI or ARB were designated as group 2 (878 patients). Results: During a follow-up of 5.90 +/- 3.39 years, 135 patients of group 1(3.1%) and 25 of group 2(2.8%) developed new-onset dementia. Group 1 and group 2 had similar proportions of new-onset dementia (p = 0.75). The Kaplan-Meier curve demonstrated that patients with ACEI or ARB were not associated with a lower incidence of dementia during the follow-up period (log rank p = 0.91). Cox-regression analysis also showed that usage of ACEI or ARB was not associated with a lower risk of new-onset dementia after adjustment for gender and comorbidities. (Hazard ratio = 0.942, 95% confidence interval 0.589 similar to 1.506, and p = 0.80). Conclusions: ACEI or ARB may be ineffective in reducing the incidence of dementia in patients with AF.