OBJECTIVES: The aims of the study were to assess and compare the social costs of subjects with cardiovascular diseases (CVD) with those of subjects without CVD. METHODS: Data were collected from a population based naturalistic prospective survey, who enrolled a sample of 3984 subjects representative of the Italian general population aged 40 to 79 years. We selected individuals with CVD defined as cerebrovascular or coronary heart (CHD) diseases. We matched each of them by age and sex with controls (1:1 ratio). We conducted a Cost of Illness analysis from a societal perspective with a 3 month time horizon. Direct medical costs (hospitalizations, drug therapies, specialist visits, diagnostics and laboratory exams) were quantified using the National Health Service tariffs expressed in Euro 2005. RESULTS: We selected 197 patients with CHD (mean age 65.3, 70.1% male) and 110 patients with cerebrovascular disease (mean age 66.0, 57.3% male), each matched with 197 and 110 separate controls. In the CHD group the mean total cost was 448 Euro-patient-month compared to Euro 128.9 for cases and controls, respectively (P<0.0001). On average, direct medical cost per patient-month was estimated at Euro 351.7 in cases and Euro 110.3 in controls (P<0.0001). In the cerebrovascular group the mean total cost was 380.4 Euro-patient-month compared to Euro 164.4 for cases and controls, respectively (P<0.0001). On average, direct medical cost per patient-month was estimated at Euro 368.6 in cases and Euro 149.8 in controls (P<0.0001). Hospitalizations accounted for the greatest proportion of healthcare costs in cases and in controls in both groups, followed by drug therapies. The working ability reduction is statistically significant higher in cases than in controls in both groups. CONCLUSION: The results of our analysis show that subjects with CVD are more costly than subjects without the diseases.