Biomarkers have emerged as interesting predictors of risk in non-ST elevation acute coronary syndromes (non-ST ACS). The aim of this study was to define the utility of the combined measurement of troponin T (TnT), C-reactive protein (CRP), NT pro-brain natriuretic peptide (NT pro-BNP) and D-dimer as biomarkers to predict adverse events. We included 358 consecutive patients admitted in two hospitals for non-ST ACS. Baseline measurements of TnT (associated with myocardial injury, positive, if > or =0.1 ng mL(-1)), CRP (a marker of inflammation), NT-proBNP (associated with left ventricular (dys)function) and fibrin D-dimer (and index of thrombogenesis) were performed. A positive CRP, NT-proBNP and D-dimer test was considered upper than the 75th percentile of our population. The risk for major events (death, new ACS, revascularization and heart failure) at 6 months' follow-up was analysed. Troponin T, NT pro-BNP and CRP were predictors of adverse events in the multivariate analysis [hazards ratio (HR): 2.00 (1.30-3.07), P = 0.0016; HR: 2.27 (1.47-3.50), P = 0.0002; HR: 1.90 (1.24-2.92), P = 0.0034 respectively], but not D-dimer levels [HR: 1.26 (0.79-2.02), P = 0.337). After adjusting for baseline characteristics and electrocardiographic changes, multimarker risk approach was associated with adverse events at 6 months, especially with the presence of three positive biomarkers [HR 2.80 (95%CI 1.68-4.68), P < 0.001]. When we divided patients by risk groups [Thrombolysis in Myocardial Infarction (TIMI) risk score], patients with two or three elevated biomarkers had higher event rates [HR 2.59 (95% CI 1.37-4.91), P = 0.004]. A multimarker approach based on TnT, CRP and NT-proBNP provides added information to the TIMI risk score in terms of ACS prognosis at 6 months, with a worse outcome for those with two or three elevated biomarkers.