The Cyprus Study is a prospective cohort study of cardiovascular disease (CVD). Its aim is to determine the relationship of intima-media thickness (IMT) of the common carotid (IMTcc), maximum thickness of IMT in the carotid bifurcation (IMTmax), number of carotid and femoral bifurcations with plaque and total plaque thickness (TPT) (sum of the maximum plaque measurements taken from the four bifurcations scanned) with the prevalence of clinical CVD. A total of 767 individuals (46% male) over the age of 40 years were recruited from a mountain village and a town outside the capital Nicosia. In addition to clinical examination, carotid and common femoral bifurcations were scanned with ultrasound. After controlling for conventional risk factors, there was little evidence of an association of IMTcc with CVD prevalence. However, IMTmax and TPT were associated with 2.9-fold (1.22 to 7.07) and 6.87-fold (2.42 to 19.43) increased odds of CVD prevalence, respectively. In conclusion, the TPT and number of bifurcations with plaque are more strongly associated with the prevalence of CVD. These findings warrant investigation in prospective studies to document associations with incident CVD events.