Chlamydia pneumoniae infection has been described as a risk factor for atherosclerosis on the basis of raised seroreactivity against complete elementary bodies among cardiovascular disease (CVD) patients. In order to identify antigens of possible pathogenetic relevance, C. pneumoniae IgG and IgA immunoblot profiles were compared for CVD patients (IgG: n = 159; IgA: n = 72) and for controls (IgG: n = 158; IgA: n = 115), all with prior C. pneumoniae infection. IgG and IgA recognition patterns were very similar, and a broad range of antigens was commonly recognized. However, statistical analysis demonstrated IgG seroresponses to 40, 54, 60, 75, and 98 kDa antigens to be more frequent among patients and resulting in odds ratios between 2.3 (98 kDa) and 29.4 (40 kDa) for development of CVD. This relation remained evident after adjustment for age and sex. Cardiovascular risk from prior chlamydial infection can thus be linked to certain antigens. Thus, for the first time potential atherogenetic virulence factors of C. pneumoniae are described. Though causal relation of chlamydial and atherosclerotic disease cannot be proven yet, evidence is growing that chlamydial structures play a part in the multifactorial pathogenesis of one of the most prevalent health hazards world-wide.