BACKGROUND: Long-term risk of post-discharge mortality associated with acute coronary syndrome remains a concern. The development of a model to reliably estimate two-year mortality risk from hospital discharge post-acute coronary syndrome will help guide treatment strategies. METHODS: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients, NCT01171404) and EPICOR Asia (EPICOR Asia, NCT01361386) are prospective observational studies of 23,489 patients hospitalized for an acute coronary syndrome event, who survived to discharge and were then followed up for two years. Patients were enrolled from 28 countries across Europe, Latin America and Asia. Risk scoring for two-year all-cause mortality risk was developed using identified predictive variables and forward stepwise Cox regression. Goodness-of-fit and discriminatory power was estimated. RESULTS: Within two years of discharge 5.5% of patients died. We identified 17 independent mortality predictors: age, low ejection fraction, no coronary revascularization/thrombolysis, elevated serum creatinine, poor EQ-5D score, low haemoglobin, previous cardiac or chronic obstructive pulmonary disease, elevated blood glucose, on diuretics or an aldosterone inhibitor at discharge, male sex, low educational level, in-hospital cardiac complications, low body mass index, ST-segment elevation myocardial infarction diagnosis, and Killip class. Geographic variation in mortality risk was seen following adjustment for other predictive variables. The developed risk-scoring system provided excellent discrimination (c-statistic=0.80, 95% confidence interval=0.79-0.82) with a steep gradient in two-year mortality risk: >25% (top decile) vs. ~1% (bottom quintile). A simplified risk model with 11 predictors gave only slightly weaker discrimination (c-statistic=0.79, 95% confidence interval =0.78-0.81). CONCLUSIONS: This risk score for two-year post-discharge mortality in acute coronary syndrome patients ( www.acsrisk.org ) can facilitate identification of high-risk patients and help guide tailored secondary prevention measures.