The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SDBP and average real variability (ARVBP, defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARVSBP and SDSBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARVSBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARVSBP: -0.006 [0.003]), and higher SDSBP with lower hippocampal fractional anisotropy (-0.02 [0.01]; all P<0.05), independent of cumulative exposure to SBP during follow-up. Conversely, cumulative exposure to SBP and diastolic BP was not associated with hippocampal volume. There was no interaction by sex or race between ARVSBP or SDSBP with hippocampal volume or integrity. In conclusion, visit-to-visit BP variability during young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife.