Background. Several mechanisms may associate tooth loss and related oral inflammation with cognitive impairment. The authors studied the relationship between tooth loss and cognitive function. Methods. The REasons for Geographic And Racial Differences in Stroke study is a national longitudinal study of more than 30,000 African American and white adults 45 years or older. Data for tooth loss, cognitive function and potential confounding variables were available for 9,853 participants at the time of analysis. The authors used incremental linear regression modeling to investigate the crosssectional association between self-reported tooth loss and cognitive function. Results. In unadjusted analysis (mean learning followed by recall; a level of significance of .05), the loss of six to 16 teeth and the loss of more than 16 teeth were associated with poorer cognitive function compared with the loss of no teeth. Attenuated associations persisted after the authors adjusted for demographic and systemic risk factors. The full model, which was adjusted for socioeconomic status (SES), revealed no association between tooth loss and cognitive function. Conclusion. Tooth loss may be associated with cognitive function; however, this association is mediated by age and SES. Clinical Implications. Tooth loss due to periodontal disease may be a marker for low SES, and the interplay of these factors with advanced age may confer risk of having poorer cognitive function. Further studies are needed to clarify these associations.