Introduction: The association between orthostatic blood pressure (BP) changes and cognitive function has not been thoroughly investigated. Moreover, whether orthostatic hypotension or hypertension modifies the effects of intensive BP control on cognitive outcomes is unknown. Hypothesis: We hypothesized that orthostatic BP changes were associated with cognitive function and the effects of intensive BP control on cognitive outcomes might be different among individuals with/without orthostatic hypotension or hypertension. Methods: We performed a post hoc analysis of SPRINT MIND, a randomized controlled trial evaluating the effects of intensive vs. standard SBP control on cognitive outcomes in hypertensive patients. The relationships between baseline orthostatic BP changes (defined as baseline standing systolic BP [SBP]–baseline seated SBP) and probable dementia (PD) and mild cognitive impairment (MCI) were analyzed. The competing risk proportional hazards regression and cubic spline regression were used in analysis. Results: A total of 8547 participants (mean [SD] age, 67.9 [9.3] years; 5543 [64.9] men) were included in this analysis. In the crude model, the restricted cubic spline analysis showed L-shaped associations between orthostatic SBP change and new-onset PD and MCI (all P for nonlinearity<0.05). However, these associations all disappeared after adjustment for covariates. Moreover, orthostatic diastolic BP change was not associated with the PD or MCI incidence. Intensive BP control did not alter the risk of PD or MCI in patients with/without orthostatic hypotension or hypertension. Conclusions: Orthostatic BP changes were not associated with the risk of PD or MCI; baseline orthostatic hypotension or hypertension did not influence the effects of intensive BP control on cognitive outcomes. These results are hypothesis-generating and merit further study.