Objective: We measured the levels of neutrophil activating peptide-2 (NAP-2) and pentraxin-3 (PTX-3) in acute coronary syndromes (ACS) patients and compared their diagnostic accuracy with cardiac troponin I (cTnI). Methods: We conducted a prospective cohort study to determine the diagnostic accuracy of PTX-3, NAP-2 and cTnI for the prediction of ACS. Consecutively eighty-three patients with sudden chest pain admitted to Dicle University Emergency Department within the first six hours of symptom onset were included in our study. Mean serum levels of PTX-3, NAP-2 and cTnI were compared between control and patient groups and ACS subgroups. Their sensitivities and specificities in early diagnosis of ACS were identified. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic validity of the markers, and areas under the ROC curve (AUC) were compared. Results: In the patient group, mean serum concentrations of NAP-2 (53.03+22.77 ng/ml) and PTX-3 (1.73+0.82 ng/ml) were considerably higher than those of the control group (24.54+9.50 and 0.50+0.39 ng/ml, respectively) (p<0.01). When compared with the control group, PTX-3 levels of all three ACS subtypes (unstable angina pectoris (USAP) - 1.62+0.41 ng/ml, non-ST elevation myocardial infarction (NSTEMI) -1.63+0.31 ng/ml and ST-elevation myocardial infarction (STEMI) - 1.75+0.89 ng/ml) were higher, whereas NAP-2 levels were higher in USAP (56.29+22.60 ng/ml) and STEMI (52.05+20.99 ng/ml) patients (p<0.01). For diagnosing ACS within the first six hours of presentation, PTX-3 sensitivity was 98.5% and specificity was 92.3%, and NAP-2 sensitivity - 98.1% and specificity - 41.3%. The ROC curve AUC values were: 0.962 for PTX-3 (95% CI 0.802 - 1.073), 0.840 for NAP-2 (95% CI 0.684 - 0.991), and 0.683 for cTnI (95% CI 0.610 - 0.940). Conclusion: Pentraxin-3 is a sensitive and specific marker for ACS diagnosis when compared with cardiac markers in patients admitted to the emergency department (ED) within the first six hours of onset of chest pain.