OBJECTIVES: To determine the effect of ACE Inhibitors/ARBs and statins on the incidence of dementia, in patients with Chronic Heart Failure (CHF). METHODS: A national retrospective cohort of Veterans Affairs (VA) patients, with at least one outpatient claim of CHF from October 1, 1996 to September 30, 2000, was identified. Drug exposure was analyzed from October 1, 1998 to September 30, 2000 and outcome of dementia (yes/no) was identified, based on ICD-9-CM codes, from October 1, 2000 to September 1, 2002. Patients with non-utilization of VA services for two years and prevalent cases of dementia were excluded. A Cox proportional hazards model of time to dementia diagnosis was constructed to test the association of drug use with dementia, adjusted for socio-demographics, co-morbidities and co-medications. RESULTS: Out of 242,734 patients, 2.77% developed dementia during follow-up. About 75% were elderly and 79% had hypertension. Females, African-Americans had significantly higher risk of dementia than males, whites, respectively. Risk of dementia increased progressively with age. In adjusted analyses, hypertension (HR: 1.157, 95% CI: 1.078-1.240), diabetes (HR: 1.105, 95% CI: 1.051-1.161), and cerebrovascular disease (HR: 1.577, 95% CI: 1.489-1.671) significantly increased risk of dementia. Adjusted analyses of one-year (HR: 0.988, 95% CI: 0.911-1.071) or two-year (HR: 0.991, 95% CI: 0.930-1.057) exposure to ACE Inhibitors did not significantly affect dementia. Adjusted analyses of one-year exposure to ARBs (HR: 0.784, 95% CI: 0.634-0.969), statins (HR: 0.906, 95% CI: 0.839-0.979) and two-year exposure to ARBs (HR: 0.711, 95% CI: 0.594-0.852), statins (HR: 0.884, 95% CI: 0.829-0.943) had protective effect on incidence of dementia. Two-year drug exposure had increased protective effect, compared to one-year exposure. CONCLUSIONS: Study suggests potential beneficial effects, to delay onset of dementia, associated with use of ARBs and statins. Thus, prescribing of such agents in pharmacotherapeutic regimens of CHF patients should be encouraged.