PurposeThe study sought to assess the performance of D-dimer testing for the diagnosis of acute coronary syndrome (ACS) and prediction of outcomes in patients admitted for suspected myocardial infarction (MI). ResultsA total of 3,557 patients with suspected ACS presenting to a single center with a broad range of symptoms including atypical chest pain were retrospectively recruited between 02/2012–01/2019.Of the study cohort, 435 patients had unstable angina (UA), 420 non-ST-segment elevation myocardial infarction (NSTEMI), 22 ST-segment elevation myocardial infarction (STEMI), and 2,680 non-coronary chest pain. Plasma D-dimer concentrations in patients with hs-cTnT > 14 ng/L differed significantly from those with hs-cTnT < 14 ng/L (1.5 ± 3.6 mg/L vs. 0.5 ± 0.8 mg/L; p < 0.0001). Positive predictive value for a final diagnosis of ACS increased proportionally to rising D-dimer concentrations. The area under the curve (AUC) to discriminate STEMI from non-coronary chest pain (AUC 0.729, 95% confidence interval [CI] 0.71–0.75) was moderate and differed not significantly to UA (AUC 0.595, 95% CI 0.58–0.61; p = 0.0653). During a median follow-up of 29 months, higher D-dimer was associated with a significantly increased risk of recurrent MI (quartile 4 vs. 1: hazard ratio [HR], 6.9 [95% CI 1.2–39.9]; p < 0.0001) and higher all-cause mortality (HR, 17.4 [95% CI 4.3–69.9]; p < 0.0001). D-dimer was an independent predictor of all-cause mortality (p < 0.0001) and subsequent MI events (p = 0.0333). ConclusionsD-dimer testing revealed great potential to provide independent prognostic information on recurrent MI and all-cause mortality. However, D-dimers do not improve the diagnostic performance except if values exceed the 95th percentile.