Periodontitis has been associated with an increased risk for atherosclerosis. Prospective data concerning its association with risk of stroke, especially those measuring systemic exposure to periodontal pathogens, are scarce. We analyzed if serum antibody levels to two major periodontopathogens predict stroke. The cases and the controls were nested in a random population-based sample of 8911 subjects aged 30-59 years at baseline, who participated in a cardiovascular disease (CVD) risk factor survey in Eastern Finland in 1977 and were followed for 15 years. CVD-free controls (n=516) were matched for sex and 5-year age group with stroke cases (n=470). In subjects free from CVD at baseline (n=893), systemic exposure to Porphyromonas gingivalis increased the risk of stroke: compared to seronegative subjects, men IgA-seropositive and women IgG-seropositive for P. gingivalis had a multivariate odds ratio (OR) (95% CI) of 1.63 (1.06-2.50) and 2.30 (1.39-3.78) for stroke, respectively. Higher OR was observed in males, who had never smoked: compared to seronegative men, P. gingivalis IgA-seropositive men had a multivariate OR of 3.31 (1.31-8.40, p=0.012) for stroke. No association between antibody levels to Actinobacillus actinomycetemcomitans and stroke was found. The results suggest that the systemic exposure to P. gingivalis may predispose to incident stroke.