Although hypertension, hypercholesterolemia and diabetes mellitus (DM) are recognized as major cardio-metabolic risk factors in primary Acute Coronary Syndrome (ACS) prevention, studies focusing on secondary ACS incidence are scarce. In the present study, the association between the aforementioned factors and 10-year ACS prognosis was evaluated. From October 2003 to September 2004 2,172 consecutive patients with ACS diagnosis, from 6 Greek hospitals, were enrolled. During 2013-14, the 10-year follow-up was performed in 1,918 participants. Baseline clinical factors were assessed through physical examination, medical records and pharmacological management. All-cause mortality and the development of fatal or non-fatal ACS events were recorded through medical records or hospital registries. Logistic regression models were applied to evaluate the impact of baseline clinical status on the ACS prognosis. The 10-year all cause and ACS mortality rate was 32.6 and 17.8%, respectively. Multi-adjusted analysis highlighted that, after taking into account various potential confounders, DM was the sole clinical factor associated with adverse effect on the 10-year ACS fatal incidence [Odds Ratio (OR)=1.35, 95% Confidence Interval (95% CI) 1.01, 1.80, p=0.04]. DM was the only clinical factor that aggravated ACS prognosis, whereas abnormal lipids profile and blood pressure did not seem to determine prognosis. Thus, glycaemic control may play a critical role in the secondary CVD prevention management of ACS patients.