The association between long-term coffee consumption and 10-year cardiovascular disease incidence among Acute Coronary Syndrome (ACS) patients was evaluated. From 2003 to 2004, 2172 ACS consecutive patients from six major Greek hospitals were enrolled. During 2013-2014, the 10-year follow-up was performed (88% participation rate) and recurrent fatal or non-fatal ACS was recorded. Baseline coffee consumption (cups/day) was assessed using a semi-quantitative Food Frequency Questionnaire. Multi adjusted analysis revealed that 1-2 cups of coffee/day versus no consumption had an adverse effect on the ACS incidence [odds ratio (OR) = 1.35, 95% confidence interval (CI) 1.01, 1.79]. In subgroup analysis, with hypertension as strata, only the normotensive reached significance. Odds ratios for 1-2 and ≥3 cups relative to no consumption were [OR = 1.66, 95% CI 1.07, 2.60] and [OR = 1.86, 95% CI 1.06, 3.27], respectively, after controlling for potential confounders. Thus, avoidance of coffee may be of high importance to ameliorate disease prognosis among cardiac patients.