Adherence to the Mediterranean diet (MD) has been reported to improve CHD prognosis and to be inversely associated with CHD mortality. The aim of the present study was to investigate the association of adherence to the MD with CHD incidence and mortality in the Greek European Prospective Investigation into Cancer and Nutrition cohort, a population with traditional Mediterranean roots. In a general population sample of 23,929 adult men and women with no CVD or cancer at enrolment, a validated FFQ was interviewer-administered, sociodemographic, physical activity and other characteristics were recorded, and arterial blood pressure and anthropometric characteristics were measured. In a median period of 10 years, 636 incident CHD cases and 240 CHD deaths were recorded. Associations of adherence to the MD, operationalised through a nine-component score (0, poor; 9, excellent), with CHD incidence and mortality were evaluated through Cox regression controlling for potentially confounding variables. A two-point increase in the MD score was associated with lower CHD mortality by 25 % (95 % CI 0.57, 0.98) among women and 19 % (95 % CI 0.67, 0.99) among men. The association of adherence to the MD with CHD incidence was again inverse, but weaker (hazard ratios 0.85 (95 % CI 0.71, 1.02) among women and 0.98 (95 % CI 0.87, 1.10) among men). With respect to score components, only meat among men (positively) and fruits and nuts among women (inversely) were associated with both the incidence of and mortality from CHD. The MD, as an integral entity, is inversely associated with CHD incidence and, particularly, mortality.