Background: Chronic kidney disease (CKD) is a factor of low response to clopidogrel. We sought to assess the functional impact of cilostazol in CKD patients with undergoing hemodialysis. Methods: Seventy-four patients with CKD undergoing hemodialysis and percutaneous coronary intervention (PCI) were enrolled. Patients were randomly assigned to receive clopidogrel (75 mg/day [group 1, n=24]), high-maintenance dose of clopidogrel (150 mg/day [group 2, n=25]), or clopidogrel (75 mg/day) with cilostazol (200 mg/day [group 3; n=25]) for 14 days. Another 50 patients with normal renal function undergoing PCI were treated with 75 mg of clopidogrel and served as the control group. Platelet function was evaluated before and after anti-platelet therapy with light transmittance aggregometry and with VerifyNowTM P2Y12 assay. Platelet activation markers (sCD40L and sP-selectin) were also assessed. Results: The baseline platelet function measurements were similar in the three groups of patients; however, the CKD groups had significantly higher platelet aggregation activity compared with the control groups. The rate of high on-treatment platelet reactivity was significantly lower in group 3 than in groups 1 and 2 (10% vs. 43% vs. 32%, respectively, p < 0.05, figure). After 14 days of anti-platelet therapy the changes in plasma sCD40L and sP-selectin levels were significantly higher in group 3 compared with groups 1 and 2 (p < 0.01); however, there were no significant differences in platelet function and activation markers between groups 1 and 2. Conclusions: Adjunctive cilostazol improves platelet inhibition compared with 75 or 150 mg of clopidogrel in CKD patients undergoing hemodialysis.