High-sensitivity cardiac troponin assays have improved the detection of acute coronary syndrome. To examine the possible incremental value of copeptin in the detection of acute coronary syndrome. We designed a prospective cohort study to compare the performance of high-sensitivity cardiac troponin T (hs-cTnT) measured at admission in combination with copeptin, and the performance of hs-cTnT alone, measured at admission, 3 hours and 6 hours, in patients with suspected acute coronary syndrome of < 6 hours' duration after onset of symptoms (exclusion of patients with ST-segment elevation myocardial infarction). Fifty-eight consecutive patients fulfilled our criteria and were included. After detailed investigations, the final adjudicated diagnosis was acute coronary syndrome in 30 patients (including acute myocardial infarction in 13 and unstable angina in 17) and non-acute coronary syndrome in 28 patients. Measured on admission, hs-cTnT concentration was > 14 ng/mL (99 th percentile) in 22 patients with acute coronary syndrome; repetition of the measurement at 3 hours and 6 hours identified three and four additional patients, respectively. The combination of copeptin with hs-cTnT determined on admission identified 26 patients with acute coronary syndrome, with a negative predicted value of 82.6%. The area under the receiver operating characteristic curve was 0.90 for hs-cTnT measured on admission, and 0.94 if repeated at 3 hours and 6 hours or combined with copeptin measurement at admission (non-significant difference). This prospective study demonstrated that a dual marker strategy that combines hs-cTnT with copeptin increased slightly the detection of acute coronary syndrome at admission.