A large-scale study was conducted to assess the effect of long-term administration of trapidil on the prognosis of patients with angiographic evidence of coronary artery disease (CAD). A large-scale, multicenter study, the Japan Multicenter Investigation for Cardiovascular Diseases-Mochida was an open-label, randomized trial of 1,743 patients with CAD who were < or =70 years old and had angiographic evidence of >25% stenosis in any coronary artery. We randomly assigned the patients to receive medical treatment either with trapidil 100 mg 3 times daily (trapidil group, n = 873) or without trapidil (control group, n = 870). The mean follow-up period was 924 days. The incidence of cardiovascular events, including cardiac death, nonfatal myocardial infarction, angina pectoris/heart failure requiring hospitalization, and cerebrovascular events was 11.1% in the trapidil group and 14.9% in the control group (relative risk 0.75, 95% confidence interval 0.58 to 0.98, p = 0.036). Thus, long-term intervention with trapidil in CAD reduces the incidence of cardiovascular events and improves the prognosis of patients with CAD.