Epidemiologic studies suggest positive associations between poor oral health and cardiovascular disease. The authors undertook a prospective study among 15,273 Swedish twins (1963-2000) to examine whether genetic factors underlying the 2 diseases could explain previous associations. They estimated hazard ratios and 95% confidence intervals controlling for individual factors and stratifying on twin pairs to control for familial effects. Quantitative genetic analyses estimated genetic correlations between oral diseases and cardiovascular disease outcomes. Tooth loss (hazard ratio (HR) = 1.2, 95% confidence interval (CI): 1.1, 1.4) and periodontal disease (HR = 1.3, 95% CI: 1.0, 1.4) were associated with small excess risks of cardiovascular disease; periodontal disease was also associated with coronary heart disease (HR = 1.4, 95% CI: 1.1, 1.6). Adjustment for genetic factors in co-twin analyses did not appreciably change estimates. In contrast, tooth loss was more strongly associated with coronary heart disease in twin models (HR = 2.1, 95% CI: 1.2, 3.8) compared with adjusting for individual factors alone (HR = 1.3, 95% CI: 1.1, 1.4). There was evidence of shared genetic factors between cardiovascular disease and tooth loss (r(G) = 0.18) and periodontal disease (r(G) = 0.29). Oral disease was associated with excess cardiovascular disease risk, independent of genetic factors. There appear to be common pathogenetic mechanisms between poor oral health and cardiovascular disease.