The present systematic review and meta-analysis assessed the strength of a reported association between elevated serum anti-periodontal bacterial antibody responses and coronary heart disease (CHD). Twenty original studies were identified after systematically searching five databases. The majority (n= 11) compared serum anti-Porphyromonas gingivalis (Pg) and/or anti-Aggregatibacter actinomycetemcomitans (Aa) IgG antibody responses between CHD patients and control participants. The strength of the association between serum anti-Pg antibodies and CHD (n= 10) and serum anti-Aa antibodies and CHD (n= 6) was investigated using a meta-analysis approach separately. Most studies (61%) reported that the serum IgG antibody responses were elevated in CHD patients than in controls. The meta-analyses showed a significant association between elevated serum IgG antibody responses (anti-Pg and anti-Aa) and CHD, with pooled odds ratios of 1.23 [95% confidence interval (CI): 1.09-1.38, p= .001] and 1.25 (95% CI: 1.04-1.47, p= .0004), respectively. A modest increase of CHD events in individuals with higher serum anti-Pg and anti-Aa IgG antibody responses may support their use as potential biomarkers to detect and monitor at-risk populations. However, the observed inconsistencies with the design and interpretation of immunoassays warrant standardization of the immunoassays assessing antibody responses against periodontal bacteria.