OBJECTIVE To determine whether visit-to-visit fasting glucose (VVFG) variability in young adulthood is associated with midlife hippocampal integrity and volume. RESEARCH DESIGN AND METHODS Multivariable-adjusted linear regression models were used to estimate the association between VVFG variability and brain MRI variables in 543 CARDIA study participants. VVFG variability was defined by the SD of FG (SDFG), the coefficient of variation of the mean FG (CVFG), and the average real variability (ARV(FG)) over 25 years of follow-up. Hippocampal integrity fractional anisotropy (FA) and tissue volume standardized to intracranial volume were measured by 3T MRI at year 25. RESULTS After multivariable adjustment, higher FG variability (1-SD increase) was associated with lower hippocampal FA (SDFG -0.015 [95% CI -0.026, -0.004]; CVFG -0.009 [95% CI -0.018, -0.001]; ARV(FG) -0.011 [95% CI -0.019, -0.002]) and lower hippocampal volume (SDFG -0.012 [95% CI -0.023, -0.001]). CONCLUSIONS Higher VVFG variability in young adulthood is associated with lower midlife hippocampal integrity and volume, suggesting its value in predicting risk for hippocampal structural damage.