Abstract Background Several biomarkers independently predict outcome following ST-segment elevation myocardial infarction (STEMI). We hypothesized that combining information from multiple circulating biomarkers with numerous pathophysiological pathways may improve biomarker risk stratification following a STEMI. Method This was a prospective study of 735 patients with STEMI treated with primary percutaneous coronary intervention. Seventeen biomarkers were drawn before revascularization, including adrenalin, noradrenalin, C-reactive protein (CRP), neutrophil gelatinase-associated lipocalin (NGAL), pro-atrial natriuretic peptide (pro-ANP), alfa-defensin, adiponectin, troponin I, hemoglobin, thrombocyte, and total leukocyte count. The primary outcome was a composite of cardiovascular death or heart failure (CVD/HF) identified by national registries. In the effort to identify the best model, the population was randomly split into two equally sized groups, a derivation cohort and a validation cohort. We used classification and regression tree (CART) analysis to develop a risk model. The identified risk model was hereafter applied to the whole cohort. Results Mean age was 63 years, 74% were male and 33% had hypertension. During a median follow-up time of 5.0 years (3.2; 5.0), we observed 185 primary events. After including all biomarkers in the initial model, the CART analysis created a risk model including pro-ANP, NGAL, and CRP (Figure 1a). The risk of CVD/HF increased incrementally with increasing risk group (Figure 1b). The risk remained significantly higher in groups 3 and 4 after multivariable adjustments (hazard ratio (HR)=3.38 [95% confidence interval (CI): 1.60; 7.16] p=0.001 and HR=6.55 [95% CI: 2.73; 15.76] p<0.001, respectively) when compared with group 1. Figure 1 Conclusion We developed a risk model based on multiple biomarkers (NGAL, CRP, and pro-ANP) determined from a CART analysis which may ease risk stratification after STEMI. Acknowledgement/Funding Sif Rasmussen received a scholarship grant from Herlev & Gentofte Hospital and the P. Carl Petersens Fond during preparation of this manuscript.