The aim of the present work was to compare the influence of classic cardiovascular disease (CVD) risk factors on the development of acute coronary syndrome (ACS) and ischemic stroke. During 2009-2010, 1,000 participants were enrolled: 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 were population-based, control subjects, 1-for-1 matched to the patients by age and gender. The following CVD risk factors were evaluated: smoking/passive smoking, family history of CVD, physical inactivity, hypertension, hypercholesterolemia, diabetes mellitus, presence of overweight and obesity, trait anxiety (assessed with the Spielberger State-Trait Anxiety Inventory form Y-2), and adherence to the Mediterranean diet (assessed by the MedDietScore). Furthermore, participants graded the perceived significance of the aforementioned factors, using a scale from 1 (not important) to 9 (very important). The risk factors with the highest effect size for ACS, as determined by the Wald criterion, were smoking and hypercholesterolemia; regarding stroke, they were anxiety and family history of CVD (all p <0.01). When the odds ratios of each factor for ACS and stroke were compared, insignificant differences were observed, except for smoking. On the basis of the participants' health beliefs, smoking and stress emerged as the most important risk factors, whereas all subjects graded passive smoking as a least important factor. In conclusion, similarities of the risk factors regarding ACS and ischemic stroke facilitate simultaneous primary prevention measures.