OBJECTIVES: To determine the association between fatigue and survival over 10 years in a population of older community-dwelling primary care patients. DESIGN: Prospective cohort study. SETTING: Medicare health maintenance organization and Veterans Affairs primary care programs. PARTICIPANTS: Older primary care patients (N=492). MEASUREMENTS: Fatigue, operationalized as feeling tired most of the time, was assessed at baseline. Mortality was ascertained from the National Death Index. Covariates included demographics, comorbidity, cognitive function, depressive symptoms, body mass index, self-rated health, functional status, and gait speed. RESULTS: Mortality rates at 10 years were 59% (123/210) for older adults with fatigue, versus 38% (106/282) for those without fatigue (P<.001). After adjustment for multiple potential confounders, participants who were tired at baseline had a greater risk of death than those who were not (hazard ratio=1.44, 95% confidence interval=1.08-1.93). CONCLUSION: A single simple question "Do you feel tired most of the time?" identifies older adults with a higher risk of mortality. Further research is needed to identify and characterize the underlying mechanisms of fatigue, to develop and test specific treatments, and to determine whether improvement leads to decreased morbidity and mortality.