Introduction: Increased awareness of the body as an interconnected entity has caused a growing interest in the relationship between oral and systemic health. An association between periodontal and cardiovascular disease has already been well established in numerous cohort, case-control, and cross-sectional studies. The biological plausibility of a similar association between endodontic disease and cardiovascular disease is high as both periodontal and endodontic infections cause chronic inflammatory reactions, involve anaerobic gram negative rods, and result in elevated systemic cytokine levels. A recent meta-analysis investigating levels of systemic inflammatory markers in patients with apical periodontitis compared to systemic marker levels in patients with healthy periapical status revealed an association between apical periodontitis and increased levels of CRP, IL-1,2,6, ADMA, and IgG, IgA and IgM. The purpose of the present study is to conduct a systematic review and meta-analysis to provide clinicians with a detailed analysis of available evidence regarding a possible association between endodontic infections and cardiovascular disease. Methods: A comprehensive literature search was undertaken to identify all studies that reported on the relationship between endodontic pathosis as identified on radiographs, self-reported histories of endodontic treatment, survival of endodontically treated teeth, and cardiovascular disease. Studies with similar study designs were grouped and a meta-analysis was performed to evaluate associations between endodontic disease and cardiovascular disease. Results: Forest plots revealed an association between endodontic disease and cardiovascular disease among the cross-sectional and case-control study categories, but not the cohort study group. Conclusion: A statistically significant association between endodontic disease and cardiovascular disease was found in case-control and cross-sectional studies according to the results of this meta-analysis. Large-scale, prospective studies with appropriate control for confounders must be undertaken to directly test for an independent relationship between endodontic and cardiovascular disease.