The authors investigated the progression of white matter hyperintensities (WMHs) in a large population of elderly men and women. After 3 years of follow-up, women had accumulated approximately twice as much deep WMH (DWMH) as men. The progression of periventricular WMH was the same for men and women. Gender differences may affect the pathogenesis of DWMH, which in turn may result in different clinical consequences in women.