© 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. Severe sepsis poses a major burden on the U.S. healthcare system. Previous epidemiologic studies have not differentiated community-acquired severe sepsis from healthcare-associated severe sepsis or hospital-acquired severe sepsis hospitalizations. We sought to compare and contrast community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis hospitalizations in a national hospital sample. Design: Retrospective analysis of severe sepsis discharges from University HealthSystem Consortium hospitals in 2012. Setting: United States. Patients: We used the criteria from Angus et al (discharge diagnoses for both a serious infection and organ dysfunction) to identify severe sepsis hospitalizations. We defined healthcare-associated severe sepsis as severe sepsis hospitalizations with an infection present at admission, where the patient was a nursing home resident, was on hemodialysis, or was readmitted within 30 days of a prior hospitalization. We defined community-acquired severe sepsis as all other severe sepsis patients with an infection present at admission. We defined hospital-acquired severe sepsis as severe sepsis patients where the documented infection was not present at admission. Interventions: None. Measurements and Main Results: Prevalence of community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis, adjusted hospital mortality, length of hospitalization, length of stay in an ICU, and hospital costs. Among 3,355,753 hospital discharges, there were 307,491 with severe sepsis, including 193,081 (62.8%) community-acquired severe sepsis, 79,581 (25.9%) healthcare-associated severe sepsis, and 34,829 (11.3%) hospital-acquired severe sepsis. Hospital-acquired severe sepsis and healthcare-associated severe sepsis exhibited higher in-hospital mortality than community-acquired severe sepsis (hospital acquired [19.2%] vs healthcare associated [12.8%] vs community acquired [8.6%]). Hospital-acquired severe sepsis had greater resource utilization than both healthcare-associated severe sepsis and community-acquired severe sepsis, with higher median length of hospital stay (hospital acquired [17 d] vs healthcare associated [7 d] vs community acquired [6 d]), median length of ICU stay (hospital acquired [8 d] vs healthcare associated [3 d] vs community acquired [3 d]), and median hospital costs (hospital acquired [$38,369] vs healthcare associated [$8,796] vs community acquired [$7,024]). Conclusions: In this series, severe sepsis hospitalizations included community-acquired severe sepsis (62.8%), healthcare-associated severe sepsis (25.9%), and hospital-acquired severe sepsis (11.3%) cases. Hospital-acquired severe sepsis was associated with both higher mortality and resource utilization than community-acquired severe sepsis and healthcare-associated severe sepsis.