Objective: To examine associations between orthostatic hypotension (OH) with dementia and long-term cognitive decline, and update previously published results in the same cohort for stroke with an additional 16 years of follow-up. Methods: We analyzed data from 11709 participants without a history of coronary heart disease or stroke who attended the baseline exam (1987-1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mmHg or a drop in diastolic BP of at least 10 mmHg, upon standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort-surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via three neuropsychological tests administered in 1990-1992, 1996-1998, and a full battery of tests in 2011-2013. Scores were summarized and reported as standard deviations (SDs). We used adjusted Cox regression and linear mixed models. Results: Over approximately 25 years, 1068 developed dementia and 842 participants had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (HR=1.54, 95% CI 1.20-1.97) and ischemic stroke (HR=2.08, 95% CI:1.65-2.62). Persons with OH had greater, though non-significant, cognitive decline over 20 years (SD=0.09, 95% CI:-0.02-0.21). Conclusions: OH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.