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Background and Objectives: Race and sex differences in the trajectory of survivors’ cognitive changes after stroke are uncertain. We measured changes in cognitive function associated with incident stroke and variability by race (black vs white) and sex, controlling for prestroke cognitive trajectories.Methods: Prospective study of 654 survivors of incident stroke and 22,969 stroke-free participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort enrolled 2003-2007 and followed through September 30, 2014. Median follow-up was 7.3 years. Changes in global cognition (Six-Item Screener [SIS]; range, 0-6; primary outcome), new learning, verbal memory, and executive function (Word-List Learning, Word-List Delayed Recall, and Animal Fluency Test) were measured using a regression discontinuity analytic approach, where the acute effect of stroke was estimated as the difference in the expected cognitive level on the day of the stroke from the modeled trajectory of cognitive functioning before the stroke and the trajectory of cognitive functioning after the stroke. These trajectories of post-baseline cognitive function were estimated after adjustment for calendar time and baseline values of socio-demographics, vascular risk factors, clinical factors, baseline cognitive score, and random effects for intercept and slope.Results: After stroke, acute declines in global cognition were greater in men compared with women (P=0.003) and also greater in blacks compared with whites (P=0.03) (Figure). Adjusted declines in SIS scores were 0.22 points (95% CI, 0.14 to 0.31) in black men, 0.13 points (95% CI, 0.06 to 0.20) in white men, 0.10 points (95% CI, 0.02 to 0.18) in black women, and 0.01 points (95% CI, -0.06 to 0.09) in white women. Secondary cognitive assessments did not differ significantly by race or sex.Conclusion: The acute declines in global cognition after stroke are greater in men compared with women and in blacks compared with whites.