Thrombin generation (TG) is an important pathogenic factor in acute coronary syndromes including acute myocardial infarction (AMI). Since the diagnostic utility of TG remains uncertain we sought to determine whether markers of TG may triage patients presenting to the Emergency Department with chest pain. Soluble plasma levels of prothrombin fragment 1+2 (F<sub>1+2</sub>), and thrombin/antithrombin III complexes (TAT) were determined by ELISA in 80 patients presenting with chest pain to the Emergency Department and compared with 20 controls. There were no differences in TG markers between patients with non-cardiac chest pain and healthy controls. Patients with unstable angina (UA), and congestive heart failure (CHF) did not differ from controls with respect to F<sub>1+2</sub>, and TAT was elevated in UA patients (6.05 ± 1.15 ng/ml, p = 0.033) when compared with controls (3.34 ± 0.20 ng/ml). Contrary to expectations, TAT levels at presentation with AMI were well below the concentrations observed in patiens with UA and CHF. Moreover, plasma F<sub>1+2</sub> levels were significantly lower than in healthy controls (0.84 ± 0.10 ng/ml versus 1.22 ± 0.11, p = 0.026). At the time of presentation to the Emergency Department, F<sub>1+2</sub> and TAT failed to suitably triage patients with chest pain. The surprisingly low levels of TG markers in AMI patients before applying intensive therapy and reperfusion strategies deserves further investigation.