Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. However, the definitions of AKI employed in studies involving patients with cirrhosis have not been standardized, lack sensitivity, and are often limited to narrow clinical settings. We conducted a multicenter, prospective observational cohort study of patients with cirrhosis and AKI, drawn from multiple hospital wards, utilizing the modern acute kidney injury network (AKIN) definition and assessed the association between AKI severity and progression with in‐hospital mortality. Of the 192 patients who were enrolled and included in the study, 85 (44%) progressed to a higher AKIN stage after initially fulfilling AKI criteria. Patients achieved a peak severity of AKIN stage 1, 26%, stage 2, 24%, and stage 3, 49%. The incidence of mortality, general medical events (bacteremia, pneumonia, urinary tract infection), and cirrhosis‐specific complications (ascites, encephalopathy, spontaneous bacterial peritonitis) increased with severity of AKI. Progression was significantly more common and peak AKI stage higher in nonsurvivors than survivors (P < 0.0001). After adjusting for baseline renal function, demographics, and critical hospital‐ and cirrhosis‐associated variables, progression of AKI was independently associated with mortality (adjusted odds ratio = 3.8, 95% confidence interval 1.3‐11.1). Conclusion: AKI, as defined by AKIN criteria, in patients with cirrhosis is frequently progressive and severe and is independently associated with mortality in a stage‐dependent fashion. Methods for earlier diagnosis of AKI and its progression may result in improved outcomes by facilitating targeted and timely treatment of AKI. (HEPATOLOGY 2013)