We sought to determine the diagnostic value of a D-dimer test for myocardial infarction (MI). The prospective cohort study was carried in the ED of a university hospital. All included patients were tested for D-dimer and cardiac troponin I (cTnI) on ED admission and additional cTnI 6 h later. AMI was retrospectively confirmed by employing the ESC-ACC-AHA-WHF 2007 universal definition. The discriminative value of D-dimer test was assessed by ROC curve analysis. Multivariate analysis was used to identify independent risk factors associated with D-dimer elevation other than MI. A total of 178 patients were included in this study. Median D-dimer levels were significantly higher in MI patients. A D-dimer value greater than 200 ng/ml was significantly associated with MI. When used alone, the test has a high sensitivity of 91.8% but a low specificity of 23.9%. Combined use of cTnI and D-dimer tests raised the sensitivity to 98.4% and helped early triage a subgroup of low risk patients. However, the test had the downside of 58% false positives. High false positives could be partly explained by the high prevalence of underlying hypercoagulable comorbidities. Diabetes mellitus with chronic renal insufficiency was identified as the strongest risk factor associated with D-dimer elevation in patients without MI. D-dimer test alone has a low diagnostic value for MI. Co-existing hypercoagulable conditions may confound the results. Combining cTnI and D-dimer tests enables early identification a low risk group of patients for MI at the cost of high false positives.