Cilostazol, a novel platelet aggregation inhibitor, inhibits intimal proliferation in animal models. We randomly assigned 41 patients with lesions suitable for directional coronary atherectomy to the cilostazol group (200 mg/day) or the aspirin (250 mg/day) group. Medication was started before directional coronary atherectomy and was continued to a 6-month follow-up. Serial quantitative coronary angiography and intravascular ultrasound study were performed. Baseline characteristics were not different between the two groups. However, the minimal lumen diameter at follow-up was larger (2.33 +/- 0.60 mm vs 1.81 +/- 0.68 mm, p = 0.016) and the percent diameter stenosis (24.5% +/- 16.6% vs 40.9% +/- 21.0%, p = 0.010) was smaller in the cilostazol group. The change in vessel area was not different, but the percent plaque area at follow-up was smaller in the cilostazol group (55.7% +/- 11.2% vs 64.5% +/- 14.5%, p = 0.044). The restenosis rate was significantly lower in the cilostazol group (0% vs 26%, p = 0.020). We conclude that cilostazol appears to have an inhibitory effect on intimal proliferation after directional coronary atherectomy and may reduce restenosis.