BACKGROUND Individuals with low levels of health literacy have less health knowledge, worse self-management of chronic disease, lower use of preventive services, and worse health in cross-sectional studies. We sought to determine whether low health literacy levels independently predict overall and cause-specific mortality. METHODS We designed a prospective cohort study of 3260 Medicare managed-care enrollees in 4 US metropolitan areas who were interviewed in 1997 to determine their demographic characteristics, chronic conditions, self-reported physical and mental health, and health behaviors. Participants also completed the shortened version of the Test of Functional Health Literacy in Adults. Main outcome measures included all-cause and cause-specific (cardiovascular, cancer, and other) mortality using data from the National Death Index through 2003. RESULTS The crude mortality rates for participants with adequate (n = 2094), marginal (n = 366), and inadequate (n = 800) health literacy were 18.9%, 28.7%, and 39.4%, respectively (P < .001). After adjusting for demographics, socioeconomic status, and baseline health, the hazard ratios for all-cause mortality were 1.52 (95% confidence interval, 1.26-1.83) and 1.13 (95% confidence interval, 0.90-1.41) for participants with inadequate and marginal health literacy, respectively, compared with participants with adequate health literacy. In contrast, years of school completed was only weakly associated with mortality in bivariate analyses and was not significant in multivariate models. Participants with inadequate health literacy had higher risk-adjusted rates of cardiovascular death but not of death due to cancer. CONCLUSIONS Inadequate health literacy, as measured by reading fluency, independently predicts all-cause mortality and cardiovascular death among community-dwelling elderly persons. Reading fluency is a more powerful variable than education for examining the association between socioeconomic status and health.