Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese and Europeans. A total of 985 participants were recruited from three cities (Hamilton, Toronto and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured. Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5% and 2%, respectively; p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm) and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and low-density lipoprotein cholesterol, higher triglycerides and lower high-density lipoprotein cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein(a), and plasminogen activator inhibitor-1. Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.