This study examines the epidemiology of sepsis in the United States from 1979 through 2000. Sepsis is a serious condition that leads to significant healthcare burden and mortality. The study analyzed data from a nationally representative sample of nonfederal acute care hospitals, using discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The results showed that sepsis incidence increased by 8.7% annually, from 164,000 cases in 1979 to 660,000 cases in 2000. Sepsis was more common in men than women and in nonwhite individuals than white individuals. Gram-positive bacteria became the predominant cause of sepsis after 1987, while fungal infections increased by 207%. The overall in-hospital mortality rate decreased from 27.8% to 17.9%, but the total number of sepsis-related deaths continued to rise. Mortality was highest among black men. Organ failure contributed significantly to mortality, with survival improving among patients with fewer than three failing organs. The average length of hospital stay decreased, and the rate of discharge to nonacute care facilities increased. The study highlights disparities in sepsis incidence and mortality among races and genders, and underscores the need for further research to understand the underlying causes of these disparities. The findings emphasize the growing burden of sepsis and the importance of accurate national data for healthcare policy and resource allocation.This study examines the epidemiology of sepsis in the United States from 1979 through 2000. Sepsis is a serious condition that leads to significant healthcare burden and mortality. The study analyzed data from a nationally representative sample of nonfederal acute care hospitals, using discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The results showed that sepsis incidence increased by 8.7% annually, from 164,000 cases in 1979 to 660,000 cases in 2000. Sepsis was more common in men than women and in nonwhite individuals than white individuals. Gram-positive bacteria became the predominant cause of sepsis after 1987, while fungal infections increased by 207%. The overall in-hospital mortality rate decreased from 27.8% to 17.9%, but the total number of sepsis-related deaths continued to rise. Mortality was highest among black men. Organ failure contributed significantly to mortality, with survival improving among patients with fewer than three failing organs. The average length of hospital stay decreased, and the rate of discharge to nonacute care facilities increased. The study highlights disparities in sepsis incidence and mortality among races and genders, and underscores the need for further research to understand the underlying causes of these disparities. The findings emphasize the growing burden of sepsis and the importance of accurate national data for healthcare policy and resource allocation.