BACKGROUND AND OBJECTIVES: Neonatal AKI is associated with poor short- and long-term outcomes. The objective of this study was to describe the risk factors and outcomes of neonatal AKI in the first postnatal week. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The international retrospective observational cohort study, Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), included neonates admitted to a neonatal intensive care unit who received at least 48 hours of intravenous fluids. Early AKI was defined by an increase in serum creatinine >0.3 mg/dl or urine output <1 ml/kg per hour on postnatal days 2-7, the neonatal modification of Kidney Disease: Improving Global Outcomes criteria. We assessed risk factors for AKI and associations of AKI with death and duration of hospitalization. RESULTS: Twenty-one percent (449 of 2110) experienced early AKI. Early AKI was associated with higher risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.7 to 4.7) and longer duration of hospitalization (parameter estimate: 7.3 days 95% confidence interval, 4.7 to 10.0), adjusting for neonatal and maternal factors along with medication exposures. Factors associated with a higher risk of AKI included: outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children's hospital. Those factors that were associated with a lower risk included multiple gestations, cesarean section, and exposures to antimicrobials, methylxanthines, diuretics, and vasopressors. Risk factors varied by gestational age strata. CONCLUSIONS: AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as "red flags" for clinicians at the initiation of the neonatal intensive care unit course. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), NCT02443389.