AIM: The 10-year incidence of cardiovascular disease (CVD) and all-cause mortality, as well as its determinants, in a sample of men and women from Greece, was evaluated. METHODS: From May 2001 to December 2002, 1514 men and 1528 women (>18y) without any clinical evidence of CVD or any other chronic disease, at baseline, living in greater Athens area, in Greece, were enrolled. In 2011-12, 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 (coronary heart disease, acute coronary syndromes, stroke, or other CVD) was defined according to World Health Organization (WHO)-International Coding Diseases (ICD)-10 criteria. RESULTS: The 10-year CVD incidence was 19.7% in men and 11.7% in women (p<0.001). Multi-adjusted analysis revealed that the determinants of CVD events were increased age (Hazard ratio (HR) per year=1.06, 95%Confidence Interval (CI): 1.04, 1.08), male sex (HR=1.40, 95%CI: 0.90, 2.19), smoking (HR=1.53, 95%CI: 1.03, 2.27), C-reactive protein levels (HR per 1mg/L=1.06, 95%CI: 1.02, 1.15), as well as adherence to Mediterranean diet (protective) (HR per 1/55 units=0.98, 95%CI: 0.95, 1.01). CONCLUSION: The burden of CVD and its related risk factors is at emerging rates, in Greece, making the need for effective public health actions, more necessary than ever before.