Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and educational level seems to be an important determinant of the disease occurrence. The aim of this work was to investigate the association between education status and 10-year incidence of CVD, controlling for various socio-demographic lifestyle and clinical factors. From May 2001 to December 2002, 1514 men and 1528 women (>18 years) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, Greece, were enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. Education status was measured in years of schooling. The 10-year incidence of CVD was 15.7% [95% confidence intervals (CI) 14.1%-17.4%], 19.7% in men and 11.7% in women (Pgender < 0.001). Age-and gender-adjusted analyses revealed that those with low education (<9 years of schooling) were 1.52 times more likely (95% CI 1.03-2.23%) to have CVD compared with those with high education (>12 years of schooling). People in the low education group had higher prevalence of hypertension, diabetes and dyslipidaemias, were more likely to be smokers and sedentary, had less healthy dietary habits, as compared with those in the high education group. When controlling for participants' medical history, smoking, dietary and lifestyle habits, low education was no longer significantly associated with CVD, illustrating the mediating effect of clinical and behavioural factors in the link between education and disease. It was of interest that low education status interacted with alcohol drinking, enhancing the adverse effect of low education on CVD risk (relative risk 1.44, 95% CI 0.94%-2.20%), after various adjustments made. In this study, it was concluded that low educational level was associated with increased CVD risk. This was mainly explained by the intermediate association of low education with unhealthy choices that consequently worsen clinical status.