We examined the association of accelerated progression of white matter hyperintensities (WMH) with mortality outcomes in 534 older subjects at risk for cardiovascular disease. Using brain magnetic resonance imaging, volume of WMH was measured 2 times in an average of 33 months apart. After the second magnetic resonance imaging, occurrence of death was recorded during 12 years of follow-up. In multivariable analyses, each mL/y increase in global WMH was associated with 1.22-fold (95% confidence interval [CI], 1.09-1.37) higher risk of all-cause mortality, 1.29-fold (95% CI, 1.06-1.56) higher risk of cardiovascular mortality, and 1.20-fold (95% CI, 1.02-1.40) higher risk of noncardiovascular mortality. Each mL/y increase in periventricular WMH was associated with 1.22-fold (95% CI, 1.08-37) higher risk of all-cause mortality and 1.24-fold (95% CI, 1.06-1.44) higher risk of noncardiovascular mortality. Conversely, deep cortical WMH was only associated with cardiovascular mortality (1.92-fold, 95% CI, 1.12-3.30). Accelerated progression of WMH is linked with mortality risk in old age. Progression of periventricular WMH associates with noncardiovascular mortality, whereas progression of deep cortical WMH associates with cardiovascular mortality.