The aim of this study is to evaluate the effect of recent depressive episodes on coronary risk, taking into account the presence of several cardiovascular risk factors and various lifestyles, and social conditions that aggregate in the Greek population.CARDIO2000 is a matched case-control study consisting of 750 patients with a first event of acute coronary syndrome and 778 cardiovascular disease-free hospitalized subjects, randomly and stratified selected from several Greek regions. Assessment of depressive symptoms, during the past month, was based on the CES-D Scale (Radloff S, 1977). 158 (21%) coronary patients and 74 (9%) controls had short-term depressive symptoms (P<0.001). A recent depressive episode increases coronary risk by 12%, after adjusting for several confounders, while the previous outcome seems to differ significantly between sexes (OR-men = 1.09 vs. OR-women = 1.19, P<0.01). The effect of the interaction between depression and various components of social class (education, occupation, income) increases the coronary risk from 55% to 132%, while the interaction with marital status increases the previous risk by 167%, in divorced/widowed men, and by 123%, in women. Also, significant additive effects were observed between depression and smoking (25% increased coronary risk per pack-year), alcohol consumption (+97%), physical inactivity (+137%) and obesity (+127%).This study showed the moderate effect of recent depression on the risk of developing non-fatal acute coronary syndromes in the investigated population. Also, sex differences and the additional effect of the interactions between short-term depressive episodes and several emerging or established cardiovascular risk factors occurred.