Periodontitis and atherosclerosis are highly prevalent chronic inflammatory diseases, and it has been suggested that periodontitis is an independent risk factor of cardiovascular disease (CVD) and that a causal link may exist between the 2 diseases. Using Danish national registers, we identified a nationwide cohort of 17,691 patients who received a hospital diagnosis of periodontitis within a 15-year period and matched them with 83,003 controls from the general population. We performed Poisson regression analysis to determine crude and adjusted incidence rate ratios of myocardial infarction, ischemic stroke, cardiovascular death, major adverse cardiovascular events, and all-cause mortality. The results showed that patients with periodontitis were at higher risk of all examined end points. The findings remained significant after adjustment for increased baseline co-morbidity in periodontitis patients compared with controls, for example, with adjusted incidence rate ratio 2.02 (95% CI 1.87 to 2.18) for cardiovascular death and 2.70 (95% CI 2.60 to 2.81) for all-cause mortality. Patients with a hospital diagnosis of periodontitis have a high burden of co-morbidity and an increased risk of CVD and all-cause mortality. In conclusion, our results support that periodontitis may be an independent risk factor for CVD.