Objectives The purpose of this study was to determine the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) in two independent samples of patients presenting with acute coronary syndromes (ACS) and normal troponin T (TnT) values. Background Recently assessment of NT-proBNP has been studied in patients with ACS. However, the clinical relevance in patients who present without troponin elevation is unclear. Methods We included 2,614 patients from two independent registries, one serving as a derivation cohort comprising patients with evident ACS (Bad Nauheim ACS registry, n = 1,131) and the other serving as a validation cohort including chest pain patients (PACS [Prognosis in Acute Coronary Syndromes] registry, n = 1,483). NT-proBNP and TnT were measured upon admission. Clinical outcome has been assessed over a 6-month period. Results In both cohorts, the mortality rate was significantly lower among TnT negative patients: 3.8% versus 8.2% (p = 0.009) in the Bad Nauheim ACS registry, and 2.8% versus 8.6% (p = 0.009) in the PACS registry. Among TnT negative patients, receiver-operating characteristics curve analysis yielded an optimal cutoff value of 474 pg/ml for NT-proBNP that was able to discriminate patients at higher risk in the Bad Nauheim ACS and PACS registries (mortality rate 12.3% vs. 1.3%, p < 0.001 and 8.5% vs. 1.5%, p < 0.001, respectively). By Kaplan-Meier analysis, patients with NT-proBNP values over 474 pg/ml were at higher risk for death in the Bad Nauheim ACS registry (log-rank 19.01, p < 0.001, adjusted hazard ratio [HR] 9.56 [95% confidence interval (CI) 2.42 to 37.7], p = 0.001) and in the PACS registry (log-rank 23.16, p < 0.001, adjusted HR 5.02 [95% CI 2.04 to 12.33], p < 0.001). Conclusions Among patients with suspected ACS considered to be at low risk because of normal troponin values, NT-proBNP above 474 pg/ml is able to discriminate individuals at higher risk. Because of its incremental prognostic value, NT-proBNP assessment should be considered in clinical routine for risk stratification of patients with normal troponin.