OBJECTIVES: Heart failure (HF) is associated with increased risk of dementia and dementia is an independent predictor of mortality and hospitalization in HF patients. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may lower the risk of dementia by regulating the renin angiotensin system in the brain. Given the significant clinical impact of dementia associated with HF and the current urgency for effective treatments to reduce the incidence of dementia, the present study examines the effectiveness of ACEIs/ARBs that are widely prescribed for the treatment of HF. METHODS: This retrospective, longitudinal study used a cohort of patients with HF identified from a local Medicare advantage prescription drug plan to examine incidence of dementia with up to 3 years of follow up period. Multivariable time dependent Cox model and inverse-probability-of-treatment weighting (IPTW) of marginal structural model were used to estimate the risk of developing dementia controlling for sociodemographic factors, comorbidities, comedications, appropriate laboratory measures, and potential time-varying confounding affected by previous treatment (hospitalization). Adjusted dementia rate ratios were estimated among current and former ACEI/ARB users, as compared with nonusers. RESULTS: The study included a total of 8062 HF patients (mean age 74.47 ±9.21 years) of which 1135 (14.08 %) patients were diagnosed with dementia during the median follow up of 22 months. Using the time dependent Cox model, the adjusted dementia rate ratios (95% confidence interval) among current and former users were 0.90 (0.70 - 1.16) and 0.89 (0.71 - 1.10). Use of IPTW resulted in similar effect estimates (95% conservative confidence interval) of 0.99 (0.74 - 1.32) among current users and 0.80 (0.59 - 1.08) for former users as compared with the nonusers. CONCLUSIONS: This study found no difference in risk of dementia among the current and former users of ACEI/ARB as compared with the nonusers in an already at-risk HF population.