Background and purpose— 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. Methods— 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. Results— 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. Conclusions— Exceptional familial longevity is associated with a lower susceptibility to white matter lesions and lacunar infarcts, but not cerebral microbleeds.