The aim of this study was to use path analysis methods to determine if health literacy mediates the relationship between race and patient activation.We performed a secondary analysis of data from a randomized controlled trial in elderly, urban, minority patients using path analysis. Path analysis was used to evaluate the mediation of race on patient activation through different variables. Several models were tested for best fit for their effects on patient activation.Across all models, significant mediation paths were identified from race to lower patient activation through health literacy. This relationship remained significant throughout alternative model testing for covariate combinations. The best-fit model included an indirect effect of sex on patient activation through health literacy indicating that the mediation effect of health literacy on patient activation was most profound for African American males. Health literacy had a bigger influence on patient activation for participants with a greater comorbidity than for those with fewer conditions. No significant direct effect was shown between race and patient activation in any of the models.Racial disparities in patient activation were fully mediated by health literacy skills.Future interventions to improve racial disparities in patient activation need to be targeted at improving health literacy.