BACKGROUND: The aim of the present work was to examine the association of depression and marital status, with the long-term prognosis of acute coronary syndrome (ACS), among a Greek sample of cardiac patients. METHODS: From October 2003 to September 2004, a sample of 2172 consecutive ACS patients from 6 hospitals was enrolled. In 2013-2014, the 10-year follow-up was performed in 1918 participants. Depressive symptoms were evaluated using the validated CES-D score (range 0-60), while marital status was classified as: single, married/cohabitants, divorced and widowed at the time of entry to the study. RESULTS: Patients in the upper tertile of CES-D (>20 score) had 41% (95%CI 14%, 75%) higher risk of ACS incidence as compared with those in the lowest (<7 score). In contrary, married patients had 29% lower risk (95%CI 6%, 46%) of ACS mortality compared with single, widowed or divorced. Multi-adjusted analysis revealed that among the 'not married' patients, 1-point increase in the CES-D score was associated with 2% (p = .02) and 4% (p = .001) higher risk of having non-fatal and fatal cardiac events, respectively. CONCLUSIONS: The present study highlights the important role of depression in the context of marital relationships among ACS patients. Secondary public health care intervention programmes are needed to improve patient outcomes and minimise disease burden in clinical and community setting.