Aims The objective of this study was to investigate the prognostic value of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with plasma NT-proBNP in patients presenting with acute chest pain in the emergency department. Methods and results We measured simultaneously plasma and urinary NT-proBNP at admission in 301 patients with acute chest pain. In our cohort, 174 patients suffered from acute coronary syndrome (ACS). A follow-up (median of 55 months) was performed regarding the endpoints all-cause mortality and major adverse cardiac events (mortality, congestive heart failure, ACS with the necessity of a coronary intervention, and stroke). Fifty-four patients died during follow-up; 98 suffered from the combined endpoint. A significant and positive correlation of urinary and plasma NT-proBNP was found (r = 0.87, P < 0.05). Patients with troponin positive ACS had significantly elevated levels of plasma and urinary NT-proBNP compared with those with unstable angina pectoris or chest wall syndrome (each P < 0.05). The highest levels of both biomarkers were found in patients with congestive heart failure (each P < 0.05). According to Kaplan-Meier analysis, plasma and urinary NT-proBNP were significant predictors for mortality and the combined endpoint in the whole study cohort and in the subgroup of patients with ACS (each P < 0.05). Regarding Cox regression analysis, plasma and urinary NT-proBNP were independent predictors for mortality and the combined endpoint (each P < 0.05). Conclusions Urinary NT-proBNP seems to provide a significant predictive value regarding the endpoints all-cause mortality and major adverse cardiac events in patients with acute chest pain and those with ACS.