Reports of the association of Chlamydia pneumoniae (C. pneumoniae) infection with coronary artery disease (CAD) are scarce in the Oriental population. We therefore conducted a case-control study to explore this issue in Taiwan. There were 242 consecutive subjects (166 men and 76 women) who underwent cardiac catheterization at the National Taiwan University Hospital Cardiac Catheterization Laboratory. Patients with CAD (n = 156) had > or = 1 coronary artery lesion of > 50% diameter stenosis on angiography. Controls (n = 86) had no demonstrable CAD angiographically. Antibodies to C. pneumoniae were tested by using an enzyme-linked immunosorbent assay. The prevalence of antibodies to C. pneumoniae was as follows: immunoglobulin-G (IgG), 50% (122 of 242 patients); immunoglobulin-A (IgA), 72% (176 of 242 patients); and either IgG or IgA, 79% (192 of 242 patients ). The odds ratio (OR) for CAD with either IgG or IgA was 1.4 (95% confidence interval [CI] 0.7 to 2.7, p = 0.31). After adjusting for the known CAD risk factors, the OR decreased to 0.8 (95% CI 0.3 to 2.1, p = 0.60). The OR for unstable angina or acute myocardial infarction with the presence of either IgG or IgA was 0.5 (95% CI 0.2 to 1.1, p = 0.08) and 0.4 ( 95% CI 0.1 to 1.0, p = 0.049) after adjusting for other risk factors. These results suggest a high prevalence of C. pneumoniae infection in Taiwan. However, C. pneumoniae infection is not associated with angiographically documented CAD, and, in contrast, is a negative predictor for the development of acute coronary syndromes.