Background: Although high-sensitivity troponins allow early diagnosis of acute myocardial infarction, their role for identification of acute coronary syndrome in patients with normal conventional troponin remains unclear. Methods and results: A total of 446 patients presenting to the emergency department with chest pain and normal troponin (common practice assays) in 2 serial samples were included. Both samples were also centrally analyzed for high-sensitivity troponin T (hs-TnT) (Roche Diagnostics, Basel, Switzerland). Detection (> 3 ng/L) and 99th percentile (≥ 14 ng/L) cutoffs of the maximum hs-TnT levels (hs-TnTmax) were considered. The end points were acute coronary syndrome diagnosis and the composite of in-hospital revascularization or 30-day cardiac events. Results: Acute coronary syndrome was adjudicated to 84 patients (19%), and 62 (14%) had the composite end point. In univariate setting, hs-TnTmax > 3 ng/L exhibited high sensitivity (87% and 92%, respectively) and negative predictive value (93% and 97%) for both end points, whereas hs-TnTmax ≥ 14 ng/L provided high specificity (90% and 89%), although low positive predictive values (40% and 33%). After adjusting for clinical (pain characteristics and risk factors) and electrocardiographic data, there was a stepped increase of risk across hs-TnTmax categories (≤ 3, > 3 but < 14, and ≥ 14 ng/L) for both end points; however, the discriminative capacity added was marginal (integrated discrimination improvement of 2.6% and 3.5%, respectively). Conclusions: Clinical and electrocardiographic data remain the most important tools for the evaluation of patients with chest pain and with no or minimal myocardial damage. The main contribution of hs-TnT is the high negative predictive value of undetectable levels (≤ 3 ng/L). © 2012 Mosby, Inc.