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Background and Objectives Increased bleeding rates with standard dose prasugrel have led to increased questions about the effectiveness and safety of the lower maintenance dose. We compared platelet inhibitory efficacy between low dose prasugrel and standard dose clopidogrel in patients on maintenance dose dual antiplatelet therapy. Subjects and Methods Forty-three patients who underwent percutaneous coronary intervention were randomized to receive 75 mg clopidogrel (n=23) or 5 mg prasugrel (n=20). Another 20 patients were allocated to 10 mg prasugrel as a reference comparison group. All patients (weight, ≥60 kg; age, <75 years) had been receiving 100 mg aspirin and 75 mg clopidogrel daily. The platelet function test was performed at baseline and 30 days after randomization. The primary endpoint was P2Y 12 reaction unit (PRU) at 30 days between 5 mg prasugrel and 75 mg clopidogrel. Results No differences in baseline PRU values were observed among the three groups. The prasugrel (5 mg) group had a significantly lower PRU value compared with that of 75 mg clopidogrel (174.6±60.2 vs. 223.4±72.9, p=0.022) group at 30 days, whereas the 10 mg prasugrel group showed a lower PRU value (71.9±34.4) compared with that of the 5 mg prasugrel (p<0.001). The rate of high on-treatment platelet reactivity (PRU >235) was significant lower in the 5 mg prasugrel group than that in the 75 mg clopidogrel group (15.0% vs. 56.5%, p=0.010). Conclusion Prasugrel (5 mg) is more potent antiplatelet therapy than 75 mg clopidogrel in non-low body weight and non-elderly patients on a maintenance dose dual antiplatelet therapy.