Introduction: Use of systemic hormone therapy has been positively associated with development of dementia. Little is known about the dose-dependent effect of vaginal estradiol on dementia risk. Methods: We assessed associations between cumulative dose of vaginal estradiol tablets and dementia in a case-control study nested in a nationwide Danish cohort of women aged 50 to 60 years at study initiation, who did not use systemic hormone therapy. Each case was age-matched to 10 female controls. Results: A total of 4574 dementia cases were matched to 45,740 controls. Cumulative use of vaginal estradiol tablets was not associated with all-cause dementia; adjusted hazard ratio 1.02 (95% confidence interval [CI] 0.89–1.18) for low dose (< 750 mcg), 1.07 (0.94–1.21) for medium dose (750–2000 mcg), and 0.93 (0.84–1.03) for high dose (> 2000 mcg). Similarly, Alzheimer's disease (AD) only was not associated with vaginal estradiol. Discussion: Exposure to vaginal estradiol tablets was not associated with all-cause dementia or AD only.