The purpose of this study was to evaluate the serological response to the recombinant phospholipase D protein of Chlamydophila pneumoniae (CpPLD) in patients with acute coronary syndromes (ACS) and infected by C. pneumoniae. We assessed 100 serum samples from ACS patients and 100 sera from healthy blood donors, all categorized by microimmunefluorescence (MIF) into subjects with presumptive C. pneumoniae infection or past exposure (only specific IgG), chronic infection (presence of specific IgG and IgA), and uninfected, unexposed subjects (MIF titer <1:32). None of the MIF-negative sera showed antibodies against CpPLD. Among MIF-positive subjects, antibodies to CpPLD were consistently found in sera of ACS patients but not in those of healthy subjects, and their titers in ACS patients were higher in subjects with both MIF IgG and IgA than in those with MIF IgG only. Additionally, we recognized an immunodominant P5 epitope in position 233-252 aa of the CpPLD protein which strongly reacted with ACS sera. These data suggest that CpPLD is a protein potentially implicated in the pathogenesis of C. pneumoniae infection. The CpPLD protein and its P5 peptide could be plausible antigens for the diagnosis of C. pneumoniae chronic infections in ACS patients.