Restenosis after percutaneous intervention remains a significant clinical problem. Although stent implantation has significantly reduced the rate of restenosis by approximately 25% to 33%, intimal hyperplasia within stents still limits long-term vessel patency. The clinical sequelea of this neointimal proliferation is more pronounced in certain patient subgroups, eg, patients with diatbetes mellitus, diffuse disease, smaller vessels, chronic total occlusions, and lesions located in saphenous vein bypass grafts. Pharmacologic agents studied to date have failed to prevent restenosis. Tranilast, a novel anti-inflammatory agent, interferes with the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor and transforming growth factor beta-1. Basic and preliminary clinical studies conducted with tranilast in Japan have shown encouraging results in terms of reducing restenosis. The Prevention of Restenosis with Tranilast and its Outcomes study (PRESTO), a double-blind, placebo-controlled study (n = 11,500), will test the efficacy of two doses (300 and 450 mg twice a day) of tranilast administered for 1 and 3 months compared with placebo. The primary objective is to compare the composite clinical event rate (death, myocardial infarction, or the need for ischemia-driven target vessel revascularization) after 9 months in patients treated with tranilast or placebo. Angiographic and intravascular ultrasound studies will be peformed in order to assess the effects of tranilast on angiographic restenosis and the volume of intimal hyperplastic tissue. If successful, tranilast will be the first drug to reduce angiographic and clinical restenosis.