Background: High-sensitivity troponin (HS-TnT) combined with copeptin have been proposed to expedite the diagnostic exclusion of acute myocardial infarction. The Global Registry of Acute Coronary Events (GRACE) has been validated and recommended by the European Society of Cardiology as a prognostic score in the management of acute coronary syndrome (ACS) without ST-segment elevation (non-ST+) on the electrocardiogram. Our study examined whether a low GRACE score (<108) combined with negative HS-TnT (<14 ng/L) and copeptin (<14 pmol/L) reliably exclude the diagnosis of non-ST+ ACS, including non-ST-segment elevation myocardial infarction and unstable angina., Methods: This observational, prospective study included patients presenting with chest pain lasting <6 hours, consistent with non-ST+ ACS. Blood was collected early for measurements of copeptin and HS-TnT. The negative predictive value of combined copeptin, HS-TnT, and GRACE score was calculated in the diagnosis of non-ST+ ACS. The thresholds of positivity were 14 ng/L for HS-TnT, 14 pmol/L for copeptin and 108 for the GRACE score., Results: Among 247 patients retained in the analysis, the diagnosis of ACS was made in 50 (20.4%), including 39 non-ST-segment elevation myocardial infarction and 11 unstable angina. The negative predictive value of combined HS-TnT, copeptin and GRACE score was 99%., Conclusion: A negative copeptin associated with a negative HS-TnT in a patient presenting with a low GRACE score expedited the diagnostic exclusion of non-ST+ ACS., (Copyright © 2014 Elsevier Inc. All rights reserved.)