On MRI, cerebral white matter lesions, lacunar infarcts, and cerebral microbleeds are common imaging correlates of cerebral small vessel damage in apparently healthy elderly individuals. We investigated whether middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, have a lower prevalence of white matter lesions, lacunar infarcts, and cerebral microbleeds than control subjects. All subjects were from the Leiden Longevity Study. In this study, middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, were contrasted to their spouses. Cerebral small vessel disease was assessed using 3-T MRI. Offspring were less likely to have severe periventricular frontal caps (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-1.1; P trend=0.01) and severe periventricular bands (OR, 0.4; 95% CI, 0.2-0.8; P trend=0.02). Moreover, offspring were less likely to have frontal (OR, 0.4; 95% CI, 0.2-0.9; P trend=0.05), parietal (OR, 0.4; 95% CI, 0.1-0.9; P trend=0.001), temporal (OR, 0.3; 95% CI, 0.1-0.8]; P trend=0.004), and occipital subcortical white matter lesions (OR, 0.3; 95% CI, 0.1-0.6; P trend=0.001). Prevalence of lacunar infarcts also was lower in offspring (OR, 0.3; 95% CI, 0.1-1.1; P=0.07). Prevalence of microbleeds was not significantly different in offspring and control subjects. Exceptional familial longevity is associated with a lower susceptibility to white matter lesions and lacunar infarcts, but not cerebral microbleeds.