We studied the association between isolated systolic hypertension (ISH) and generalized atherosclerosis as indicated by intima-media wall thickness (IMT) of the distal common carotid artery. The Rotterdam Elderly Study is a single-center study of a cohort of 11,854 elderly persons >55 years old. Baseline measurements included ultrasonic evaluation of plaques and vessel wall thickness of both carotid arteries and extensive measurements of cardiovascular risk factors. Mean IMT and lumen diameter of subjects with ISH (systolic pressure >160 mm Hg and diastolic pressure <90 mm Hg) among the first 1,000 participants (n=33) and 66 ageand sex-matched control subjects were compared. None of the subjects were using antihypertensive drug treatment, and all were free of cardiovascular disease. Mean IMT of the right common carotid artery was significantly higher in those with ISH than in normotensive subjects, with a mean difference of 0.07 mm (95% confidence interval [CI], 0.01, 0.14). Results for the left carotid artery were similar (mean difference, 0.06 mm; 95% CI, −0.01, 0.13). The end-diastolic mean lumen diameter was significantly larger in subjects with ISH than in control subjects for both right and left sides, with a mean difference of 0.70 mm (95% CI, 0.38, 1.01) and 0.48 mm (95% CI, 0.17, 0.80), respectively. Adjustment for differences in body mass index, serum lipids, smoking, and fibrinogen did not materially change the findings. Furthermore, atherosclerotic plaques were more frequently observed among those with ISH compared with control subjects, with a mean difference of 12% (95% CI, -1, 25). Our findings suggest that generalized atherosclerosis, ultrasonographically determined as increased carotid IMT, is associated with ISH in asymptomatic elderly subjects.