This article systematically reviews U.S. studies examining the prevalence of limited health literacy and evaluates demographic associations in pooled analyses. The review includes 85 studies with data on 31,129 subjects, reporting a prevalence of low health literacy between 0% and 68%. Pooled analyses reveal a weighted prevalence of low health literacy of 26% (95% CI, 22% to 29%) and marginal health literacy of 20% (95% CI, 16% to 23%). The prevalence of low health literacy is associated with education level, ethnicity, and age but not gender or measurement instrument. The review highlights the importance of simplifying health services and improving health education to address health disparities and improve the health of Americans.This article systematically reviews U.S. studies examining the prevalence of limited health literacy and evaluates demographic associations in pooled analyses. The review includes 85 studies with data on 31,129 subjects, reporting a prevalence of low health literacy between 0% and 68%. Pooled analyses reveal a weighted prevalence of low health literacy of 26% (95% CI, 22% to 29%) and marginal health literacy of 20% (95% CI, 16% to 23%). The prevalence of low health literacy is associated with education level, ethnicity, and age but not gender or measurement instrument. The review highlights the importance of simplifying health services and improving health education to address health disparities and improve the health of Americans.