BACKGROUND: We sought to compare the platelet responsiveness to clopidogrel or cilostazol between patients with chronic renal failure (CRF) and those with normal renal function. METHODS: We conducted a prospective, randomized, open-label, two-center trial. In protocol A, total of 23 patients with normal renal function received a daily dose of 75 mg of clopidogrel (group I). Also, 36 patients with CRF were divided into 2 groups according to daily dose of clopidogrel: 75 mg for 30 days (group II, n = 18) or 150 mg (group III, n = 18). In protocol B, a total of 63 patients with CRF undergoing hemodialysis were enrolled. Patients were randomly assigned to receive either a daily dose of 75 mg of clopidogrel for 14 days (group I, n = 21) or a daily dose of 150 mg (group II, n = 22) or a daily dose of 75 mg of clopidogrel with 200mg of cilostazol (group III; n = 20) and control normal renal function (group IV; n=20). Platelet responsiveness was assessed at baseline and after treatment with conventional light aggregometry and verifyNow. RESULTS: In protocol A, a significant difference was found in the P2Y12 reaction unit value among the 3 groups (239짹87 in group I, 308 짹 70 in group II, 302 짹 81 in group III (p = 0.013) and in the percentage of inhibition (p = 0.026) after treatment. No significant difference was found between groups II and III. In protocol B, baseline platelet function measurements were similar in 3 CRF groups. After treatment, percent inhibition of 5 關mol/l ADP induced maximal platelet aggregation was significantly different among the 3 groups (47.4 짹 15.8 in group I, 44.7 짹 14.2 in group II, 26.3 짹 17.7 in group III, p=0.015, figure 1). Percent inhibition of 20 關mol/l ADP was consistently different (60.4 짹 16.8 in group I, 55.9 짹 12.2 in group II, 37.2 짹 12.7 in group III, p=0.026, figure 2). CONCLUSION: Adjunctive cilostazol improves platelet inhibition as compared with conventional or high maintenance dose of clopidogrel in patients with CRF.