Background and Purpose— Carotid plaques and elevated carotid artery intima-media thickness (IMT) are major predictors of vascular morbidity and mortality. Our aim was to test their association with 2 polymorphisms of the apolipoprotein E ( apoE ) gene, ε and -219G/T. Methods— The study was performed on 5856 subjects aged ≥65 years recruited from the French population for the Three-City Study. Carotid ultrasound examination included an assessment of atherosclerotic plaques in the extracranial carotid arteries and a measurement of IMT in the common carotid arteries (CCA) at a site free of plaques. The genetic association was tested using genotype and haplotype analyses. Results— In a multivariate analysis including both polymorphisms and vascular risk factors, carotid plaques were more frequent in ε4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in ε2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with ε3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the ε34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the ε33 genotype, P =0.002), but the association disappeared after excluding subjects with carotid plaques. No association was found between the -219 polymorphism and either carotid plaques or CCA-IMT, and there was no interaction or cis-effect between -219 and ε. Conclusions— This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE ε polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.