The goal of the study was to examine the differences in trajectories of change in the volume of white matter hyperintensities (WMH) in healthy adults within a relatively short period. We measured volumes of periventricular and deep WMH in frontal, temporal, parietal, and occipital lobes of healthy volunteers (age 49–83) on 3 occasions, approximately 15 months apart. At baseline, 40 participants underwent magnetic resonance imaging (MRI), 37 returned for the first and 30 for the second follow-up. Latent growth curve models estimated the variance and mean change in WMH volume and examined their associations with age, sex, education, and hypertension. In both regions and for both WMH types, the positive association between volume and age was stronger among the middle-aged adults and became weaker in older ages, as a logarithmic function of age. Individual variations were present in initial WMH volume but not in WMH volume progression. Frontal deep WMH volume was greater in hypertensive participants, whereas lower education was associated with greater posterior deep WMH volume. Thus, white matter of healthy middle-aged and older adults undergoes significant regional deterioration in a relatively short period, and is negatively affected by vascular risk and lower educational level.