© 2015 The Author(s). Background/Aims: Acute kidney injury (AKI) frequently occurs in hospitalized patients. In this study, we determined prehospitalization characteristics associated with AKI in community-dwelling adults hospitalized for a serious infection. Methods: We used prospective data from 30,239 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of community-dwelling adults ≥45 years old. We identified serious infection hospitalizations between 2003 and 2012. Using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, we defined AKI as an increase in serum creatinine (sCr) ≥0.3 mg/ dl from the first inpatient sCr measurement during the first 7 hospitalization days. We excluded individuals with a history of renal transplant or preexisting end-stage renal disease as well as individuals with <2 sCr measurements. We identified baseline characteristics (sociode-mographics, health behaviors, chronic medical conditions, biomarkers, and nonsteroidal anti-inflammatory, statin, or antihypertensive medication use) independently associated with AKI events using multivariable generalized estimating equations. Results: Over a median followup of 4.5 years (interquartile range 2.4–6.3), we included 2,074 serious infection hospitalizations among 1,543 individuals. AKI occurred in 296 of 2,074 hospitalizations (16.5%). On multivariable analysis, prehospitalization characteristics independently associated with AKI among individuals hospitalized for a serious infection included a history of diabetes [odds ratio (OR) 1.38; 95% CI 1.02–1.89], increased cystatin C (OR 1.73 per SD; 95% CI 1.20–2.50), and increased albumin-to-creatinine ratio (OR 1.19 per SD; 95% CI 1.007–1.40). Sex, race, hypertension, myocardial infarction, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and the use of nonsteroidal anti-inflammatory, statin, or antihypertensive medications were not associated with AKI. Conclusions: Community-dwelling adults with a history of diabetes or increased cystatin C or albumin-to-creatinine ratio are at increased risk for AKI after hospitalization for a serious infection. These findings may be used to identify individuals at high risk for AKI.