BACKGROUND: The aim of the study was to estimate risk factors for hospitalization due to sepsis and to determine whether these risk factors vary by age and gender. METHODS: We performed a population-based case-control study of all adult patients admitted to a medical ED from September 2010 to August 2011. Controls were sampled within the hospital catchment-area. All potential cases were manually validated using a structured protocol. Vital signs and laboratory values measured at arrival were registered to define systemic inflammatory response syndrome and organ dysfunction. Multivariable logistic regression was used to elucidate which predefined risk factors were associated with an increased or decreased risk hospitalization due to sepsis. RESULTS: A total of 1713 patients were admitted with sepsis of any severity. The median age was 72 years (interquartile range: 57-81 years) and 793 (46.3%) were male. 621 (36.3%) patients were admitted with sepsis, 1071 (62.5%) with severe sepsis and 21 (1.2%) with septic shock. Episodes with sepsis of any severity were associated with older age (85+ years adjusted OR 6.02 [95%CI: 5.09-7.12]), immunosuppression (4.41 [3.83-5.09]), alcoholism-related conditions (2.90 [2.41-3.50]), and certain comorbidities: psychotic disorder (1.90 [1.58-2.27]), neurological (1.98 [1.73-2.26]), respiratory (3.58 [3.16-4.06]), cardiovascular (1.62 [1.41-1.85]), diabetes (1.82 [1.57-2.12]), cancer (1.44 [1.22-1.68]), gastrointestinal (1.71 [1.44-2.05]) and renal (1.46 [1.13-1.89]). The strength of the observed associations for comorbid factors was strongest among younger individuals. CONCLUSIONS: Hospitalization due to sepsis of any severity was associated with several independent risk factors, including age and comorbid factors.