To determine the relationship between long-term mortality and acute kidney injury (AKI) during hospitalization after major surgery. AKI is associated with a risk of short-term mortality that is proportional to its severity; however the long-term survival of patients with AKI is poorly studied. This is a retrospective cohort study of 10,518 patients with no history of chronic kidney disease who were discharged after a major surgery between 1992 and 2002. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification, which requires at least a 50% increase in serum creatinine (sCr) and stratifies patients into 3 severity stages: risk, injury, and failure. Patient survival was determined through the National Social Security Death Index. Long-term survival was analyzed using a risk-adjusted Cox proportional hazards regression model. In the risk-adjusted model, survival was worse among patients with AKI and was proportional to its severity with an adjusted hazard ratio of 1.18 (95% confidence interval [CI], 1.08-1.29) for the RIFLE-Risk class and 1.57 (95% CI, 1.40-1.75) for the RIFLE-Failure class, compared with patients without AKI (P < 0.001). Patients with complete renal recovery after AKI still had an increased adjusted hazard ratio for death of 1.20 (95% CI, 1.10-1.31) compared with patients without AKI (P < 0.001). In a large single-center cohort of patients discharged after major surgery, AKI with even small changes in sCr level during hospitalization was associated with an independent long-term risk of death.