We conducted a nested case-control study to evaluate the relationship between antihypertensive agent class and the incidence of initial cardiovascular events. A total of 7.443 patients being treated with an antihypertensive agent in 1985-1986 were enrolled for follow-up of up to 5 years. A total of 362 patients (186 males and 176 females) developed cardiovascular events. Age (5-year interval) and sex-matched controls were then randomly selected. A Multiple logistic regression analysis was done to control for the effects of confounding factors. The results showed that the use of diuretics and beta-blockers was associated with a reduced risk of cardiovascular events (odds ratio [OR] =0.65, 95% confidence interval [CI]: 0.49-0.86, and OR=0.75, 95% CI: 0.56-1.02, respectively), against a significantly raised risk associated with the use of calcium antagonists (OR=1.34, 95% CI: 1.03-1.80). However, as far as stroke was concerned, there was no significant association of risk with the use of any agent. The control group was found to be similar to the case group with respect to the changes in the treatment program during the follow-up period. The results suggest that the calcium antagonists used in Japan during the period of 1985-1990 constituted a potential risk for the occurrence of cardiovascular events.