Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient's cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.