BACKGROUND: High on-treatment platelet reactivity (HPR) under clopidogrel treatment is frequently observed in hemodialysis (HD) patients. In such patients, 10mg of prasugrel has reportedly inhibited platelet reactivity more adequately compared with 75mg of clopidogrel. However, the efficacy of 3.75mg prasugrel in Japanese HD patients is largely unknown. METHODS: A total of 41 Japanese coronary artery disease patients under HD who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75mg prasugrel. At day 14, prasugrel was switched to clopidogrel. Platelet reactivity was measured using VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as HPR. RESULTS: The PRU level on prasugrel therapy was significantly lower than that on clopidogrel therapy before switching (219.1±62.3 PRU vs. 238.2±68.0 PRU, p=0.02). Although the prevalence of HPR was numerically lower on prasugrel therapy compared with clopidogrel therapy before and after switching, the differences did not reach a statistical significance (57.6% vs. 75.7% vs. 74.2%, p=0.13). Even under prasugrel treatment, more than half of patients showed HPR. CONCLUSIONS: Although low-dose prasugrel had somewhat better antiplatelet effect than clopidogrel, it could not significantly improve the prevalence of HPR in Japanese HD patients. Higher doses of prasugrel might be needed to achieve adequate platelet inhibition in this high thrombotic risk population.