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The economic burden of acute kidney injury (AKI) is not well understood.To estimate the effects of AKI on hospitalization costs and length of stay (LOS).Using data from the 2012 National Inpatient Sample, we compared hospitalization costs and LOS with and without AKI. We used a generalized linear model with a gamma distribution and a log link fitted to AKI to adjust for demographics, hospital differences, and comorbidities.United States29,763,649 adult hospitalizations without endstage renal disease.AKI determined using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes.Hospitalization costs and LOS.AKI was associated with an increase in hospitalization costs of $7933 (95% confidence interval [CI], $7608-$8258) and an increase in LOS of 3.2 (95% CI, 3.2-3.3) days compared to patients without AKI. When adjusted for patient and hospital characteristics, the associated increase in costs was $1795 (95% CI, $1692-$1899) and in LOS, it was 1.1 (95% CI, 1.1-1.1) days. Corresponding results among patients hospitalized with AKI requiring dialysis were $42,077 (95% CI, $39,820-$44,335) and 11.5 (95% CI, 11.2-11.8) days and $11,016 (95% CI, $10,468-$11,564) and 3.9 (95% CI, 3.8-4.1) days. AKI was associated with higher hospitalization costs than myocardial infarction and gastrointestinal bleeding, and costs were comparable to those for stroke, pancreatitis, and pneumonia.In the United States, AKI is associated with excess hospitalization costs and prolonged LOS. The economic burden of AKI warrants further attention from hospitals and policymakers to enhance processes of care and develop novel treatment strategies.