Background and purpose: Periodontal disease results in tooth loss, may contribute to systemic inflammation, and is associated with stroke. We examined cross-sectional associations between tooth loss, inflammation markers, stroke, race, and geographic region among participants in the reasons for geographic and racial differences in stroke (REGARDS) study of whites and blacks ≥45 years. Methods: We studied 24,393 participants. Associations of tooth loss and inflammation markers (C-reactive protein (CRP), white blood cell count (WBC) and albumin) were examined by linear regression, and associations of tooth loss with geographic region, race, and prevalent stroke by logistic regression. Results: Compared to whites, blacks had an odds ratio of 1.48 (95% confidence interval 1.37-1.60) of having more teeth lost. There were no geographic differences in tooth loss. Compared to no tooth loss, those with 17-32 teeth lost had 1.17 mg/L higher CRP (p < 0.0001) and 0.18 × 109/L higher WBC (p = 0.008), did not differ in albumin, and had an odds ratio of prevalent stroke of 1.28 (1.09-1.49). Those with 1-16 teeth lost did not differ in CRP and WBC, had 0.03 g/dL higher albumin (p = 0.004), and had no increased stroke prevalence. CRP or WBC did not attenuate associations between tooth loss and stroke. Conclusions: Tooth loss, which varied with race, but not region of residence, was associated with inflammation markers and stroke. The latter association was not confounded by inflammation markers. © 2008 Elsevier Ireland Ltd. All rights reserved.