At least four definitions of AKI have recently been proposed. This study sought to characterize the epidemiology of AKI according to the most recent consensus definition proposed by the Kidney Disease Improving Global Outcomes (KDIGO) Work Group, and to compare it with three other definitions. This was a retrospective cohort study of 31,970 hospitalizations at an academic medical center in 2010. AKI was defined and staged according to KDIGO criteria, the Acute Dialysis Quality Initiative's RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and a definition based on a model of creatinine kinetics (CK). Outcomes of interest were incidence, in-hospital mortality, length of stay, costs, readmission rates, and posthospitalization disposition. AKI incidence was highest according to the KDIGO definition (18.3%) followed by the AKIN (16.6%), RIFLE (16.1%), and CK (7.0%) definitions. AKI incidence appeared markedly higher in those with low baseline serum creatinine according to the KDIGO, AKIN, and RIFLE definitions, in which AKI may be defined by a 50% increase over baseline. AKI according to all definitions was associated with a significantly higher risk of death and higher resource utilization. The adjusted odds ratios for in-hospital mortality in those with AKI were highest with the CK definition (5.2; 95% confidence interval 95% CI, 4.1 to 6.6), followed by the RIFLE (2.9; 95% CI, 2.2 to 3.6), KDIGO (2.8; 95% CI, 2.2 to 3.6), and AKIN (2.6; 95% CI, 2.0 to 3.3) definitions. Concordance in diagnosis and staging was high among the KDIGO, AKIN, and RIFLE definitions. The incidence of AKI in hospitalized individuals varies depending on the definition used. AKI according to all definitions is associated with higher in-hospital mortality and resource utilization. AKI may be inappropriately diagnosed in those with low baseline serum creatinine using definitions that incorporate percentage increases over baseline.