Although patients with medically treated vasospastic angina have a good outcome, few data exist regarding the role of underlying lesion severity associated with or without hyperlipidemia in the prognosis. Therefore, the aim of the present study was to assess the relationship between the long-term outcome of vasospastic angina and the factors influencing its prognosis. A total of 256 patients (219 men, 37 women; mean age, 54.1+/-9.2) who had coronary spasm with or without underlying lesions and were being treated with calcium channel antagonists were enrolled and followed for 13.6+/-3.7 years. Cardiac events consisted of cardiac death and ischemic events, which included acute myocardial infarction and unstable angina. Cox analysis selected coronary artery stenosis (CAS, >/=50%) and risk factors such as age, hypertension, diabetes mellitus, low-density lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The presence of significant CAS was an independent predictor of event-free survival (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In 193 patients without significant CAS, there were 10 cases of cardiac death (5.2%, p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6, p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free survival in patients with than in those without lesions (p<0.0001 by log-rank test). These results demonstrate that the most important factor for long-term prognosis of vasospastic angina treated with calcium channel antagonists is significant CAS. High LDL-C, which might alter the underlying coronary endothelial function and/or accelerate atherosclerotic lesions, could also contribute to the occurrence of cardiac events, particularly in patients without significant CAS.