RATIONALE: Most cases of acute kidney injury (AKI) resolve within 72 h. However, a small number of patients with persistent severe AKI have significantly worse outcomes. We sought to describe the occurrence, impact on outcome and risk factors associated with persistent severe AKI in critically ill patients using a standardized definition. METHODS: Retrospective cohort study, investigating critically ill patients admitted to one of 16 hospitals from October 2010 to June 2018. We defined persistent severe AKI as Kidney Disease: Improving Global Outcomes stage 2-3 AKI that progressed to and persisted at stage 3 for ≥ 72 h. Risk factors for persistent severe AKI and its association with outcomes were assessed using the super learner algorithm, integrating LASSO logistic regression and XGBoost, and multivariate logistic regression or Cox proportional hazards models, using no persistent severe AKI as the comparator. MEASUREMENTS AND MAIN RESULTS: Of 65,119/190,550 (34.2%) patients with stage 2-3 AKI, 8,059 (12.4%) had persistent severe AKI. Severe, early community-acquired AKI, high fluid balance, multiple organ dysfunction, sepsis and shock were important risk factors. Persistent severe AKI was associated with an increased risk of 90-day mortality (HR 1.5, 95% CI 1.4-1.6), hospital readmission (OR 2.0, 95% CI 1.8-2.3), and with a lower probability of renal recovery (OR 0.14, 95% CI 0.13, 0.15). CONCLUSIONS: Persistent severe AKI is an uncommon, but important complication in critically ill patients, associated with an increased risk of renal non-recovery, hospital readmission and death, and an important target for therapeutic development.