Sepsis is an increasingly common and lethal medical condition that occurs in people of all ages. The influence of age on sepsis risk and outcome is incompletely understood. We sought to determine the independent effect of age on the incidence, severity, and outcome of adult sepsis. Longitudinal observational study using national hospital discharge data. Approximately 500 geographically separated nonfederal acute care hospitals in the United States. Patients were 10,422,301 adult sepsis patients hospitalized over 24 yrs, from 1979 to 2002. None. Incident sepsis cases were age adjusted and characterized by demographics, sources and types of infection, comorbid medical conditions, and hospital discharge status. Elderly patients (> or = 65 yrs of age) accounted for 12% of the U.S. population and 64.9% of sepsis cases, yielding a relative risk of 13.1 compared with younger patients (95% confidence interval, 12.6-13.6). Elderly patients were more likely to have Gram-negative infections, particularly in association with pneumonia (relative risk, 1.66; 95% confidence interval, 1.63-1.69) and to have comorbid medical conditions (relative risk, 1.99; 95% confidence interval, 1.92-2.06). Case-fatality rates increased linearly by age; age was an independent predictor of mortality in an adjusted multivariable regression (odds ratio, 2.26; 95% confidence interval, 2.17-2.36). Elderly sepsis patients died earlier during hospitalization, and elderly survivors were more likely to be discharged to a nonacute health care facility. The incidence of sepsis is disproportionately increased in elderly adults, and age is an independent predictor of mortality. Compared with younger sepsis patients, elderly nonsurvivors of sepsis die earlier during hospitalization and elderly survivors more frequently require skilled nursing or rehabilitative care after hospitalization. These findings have implications for patient care and health care resource prioritization and provide insights for expanded scientific investigations and potential patient interventions.