(The role that oral conditions may play as risk factors or indicators for various medical outcomes, including mortality, is not well understood. We have examined the relationship of periodontal disease to mortality from all causes in the VA Dental Longitudinal Study and Normative Aging Study, a prospective cohort study of the determinants of disease in aging men. Subjects were screened for entry into the closed-panel cohort in the mid-1960s, based on good medical health. They are not VA patients. We have used proportional hazards regression models to assess the relationship of periodontal health status at baseline to all-cause mortality over a 25+-year follow-up period. A total of 804 dentate subjects who were alive and medically healthy through their first follow-up exam were used in the analysis; of these, 166 died during subsequent follow-up through December 1996. Survival was calculated in years from baseline exam to death or censoring (most recent study examination date). To define periodontal health status at baseline, we separately used radiographic alveolar bone loss (ABL) (person-level scores of mean whole-mouth % ABL, measured with a Schei ruler using full-mouth series of periapical films) and periodontal clinical probing depths. Covariates included age at baseline, and assessments at baseline of smoking and alcohol use, education, body mass index, serum cholesterol, white blood cell count, blood pressure, family history of heart disease, and number of teeth present. We found that periodontal status at baseline was a significant and independent predictor of mortality in this cohort, while controlling for other recognized predictors in multivariate models. For each 20% increment in mean whole-mouth ABL, the subject's risk of death increased by 51% (RR = 1.51; 95% CI = 1.11-2.04). The increase in risk attributable to periodontal status was found to be similar in magnitude to, and independent of that attributable to cigarette smoking in this cohort. While the increased risk due to smoking was 1.52-fold (95% CI = 1.06-2.19), being in the population quintile with highest ABL scores (i.e., worst periodontal status) was associated with a 1.85 fold increase in risk (95% CI = 1.25-2.74) using multivariate analyses. The hypothesis that chronic oral infections, as in periodontitis, may have important systemic sequelae merits further investigation in prospective controlled studies.