OBJECTIVE We investigated whether family history of stroke or coronary heart disease (CHD) is associated with presence of carotid artery stenosis (CAS). METHODS The study cohort included 864 patients (72±8 years; 68% men) with CAS and 1698 controls (61±11 years; 55% men) referred for noninvasive vascular testing. CAS was defined as ≥70% stenosis in the internal carotid artery on ultrasound or history of carotid revascularization. Controls did not have CAS or history of cerebrovascular disease or CHD. Family history of stroke and CHD was defined as having ≥1 first-degree relative who had stroke or CHD before age 65 years. Logistic regression analysis was used to evaluate whether family history of stroke or CHD was associated with presence of CAS, independent of conventional risk factors. RESULTS Family history of stroke and CHD was present more often in patients with CAS than in controls, with a resulting odds ratios (95% confidence interval) of 2.02 (1.61-2.53) and 2.01 (1.70-2.37), respectively. The associations remained significant after adjustment for age, sex, body mass index, smoking, diabetes mellitus, hypertension, and dyslipidemia; odds ratios: 1.41 (1.06-1.90) and 1.69 (1.35-2.10), respectively. A greater number of affected relatives with stroke or CHD was associated with higher odds of CAS; adjusted odds ratios: 1.25 (0.91-1.72) and 1.46 (1.14-1.89) versus 2.65 (1.35-5.40) and 2.13 (1.57-2.90) for patients with 1 and ≥2 affected relatives with stroke and CHD, respectively. CONCLUSIONS Family history of stroke, and of CHD were each associated with CAS, suggesting that shared genetic and environmental factors contribute to the risk of CAS. We show that (1) family history of stroke or CHD is independently associated with presence of CAS; (2) sibling history of stroke or CHD confers greater risk than parental history; and (3) the magnitude of the association is greater in those with greater number of affected relatives, independent of the size of the family [corrected].