Background: Prasugrel, as compared to clopidogrel significantly reduced the incidence of ischemic events in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this platelet function study was to compare the antiplatelet efficacy determined with the VerifyNow P2Y12 point-of-care assay between new dual antiplatelet therapy and classic triple antiplatelet therapy in patients with STEMI undergoing primary coronary percutaneous coronary intervention (PCI) with drug-eluting stents. Methods: Twenty six patients with STEMI who were candidate for primary PCI were prospectively randomized to dual antiplatelet therapy (Aspirin, Prasugrel, n=12) or triple therapy (Aspirin, Clopidogrel, and Cilostazol, n=14) immediately after hospital arrival. Point-of-care assay was taken at the time of primary PCI, discharge and 30 days after randomization. The primary endpoint was P2Y12 reaction unit (PRU) at the time of discharge. Results: Patients with dual therapy, as compared to those with triple therapy, showed barely significant lower PRU values at the time of discharge (88.0 짹 55.3 vs. 146.1 짹 95.9, p=0.06). PRU values at 30 days was lower in patients with dual therapy compared to those with triple therapy (93.87 짹 49.97 vs. 117.60 짹 109.84) although the difference was not statistically significant (p=0.58). Percent inhibition at the time of discharge was significantly higher in patients with dual therapy compared to those with triple therapy (72.8 짹 14.15% vs. 55.9 짹 26.4%, p=0.05). Percent inhibition at 30 days was not different between the two groups (68.7 짹 15.4% vs. 63.4 짹 31.0%, p=0.64). Conclusion: A new dual therapy with aspirin and prasugrel is likely to be more potent antiplatelet combination than classic triple therapy especially in acute phase of STEMI.