Ibuprofen is widely used in children worldwide, especially in children with cancer, fever or trauma. However, large and high-quality studies on the association between ibuprofen and acute kidney injury (AKI) in children have been lacking. We aim to estimate the effect of ibuprofen on the risk of hospital-acquired AKI (HA-AKI) in a large cohort of hospitalized children in China. The Epidemiology of AKI in Chinese Hospitalized patients (EACH2 study) is a multicenter, retrospective study of 3,044,024 patients admitted from 2013 to 2015 at 25 academic medical centers in China. Patient-level data were obtained from the electronic hospitalization information system. We included 50,420 hospitalized children aged between 1 month to 18 years who had at least one SCr test during the first 3 days and any interval between two continuous SCr testing <14 days during the first 30 days of hospitalization, excluding those with end-stage renal disease, community-acquired AKI, insufficient SCr testing and without prescription. AKI was defined as an increase in SCr by 26.5 μmol/L within 48 hours or a 50% increase in SCr from the baseline. We estimated the effect of exposure to ibuprofen on the risk of HA-AKI using a COX proportional hazard model with adjustment for age, sex, standardized baseline creatinine, comorbidities, clinical procedures, other nephrotoxic drugs use and stratification by hospital and division. In the model, exposure to ibuprofen and other nephrotoxic drugs as well as operations were coded as time-varying variables. We also compared the effect sizes of ibuprofen among subgroups stratified by age, gender, chronic kidney disease, need for intensive care and exposure to other nephrotoxic drugs. Among 50,420 children who met the inclusion and exclusion criteria, 5,526 (11.0%) were ibuprofen users, and 3,476 (6.9%) had HA-AKI during hospitalization. Characteristics of hospitalized children were showed in Table 1. Ibuprofen use was associated with significantly increased risk of HA-AKI (hazard ratios,1.23; 95% CI, 1.14-1.34) after adjusting for confounders (Table 2). The greater nephrotoxicity of ibuprofen was observed in children who had chronic kidney disease, required intensive care, or were of elder age (Table 3). Abbreviation: IQR, Inter quartile range; SCr, serum creatinine; PPIs, proton pump inhibitors; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker. a: Adjusted age, sex, standardized baseline creatinine, comorbidities, clinical procedures, other nephrotoxic drugs use and stratified by hospital and division. a: Adjusted age, sex, standardized baseline creatinine, comorbidities, clinical procedures, other nephrotoxic drugs use and stratified by hospital and division. Ibuprofen was widely used and associated with an increased risk of HA-AKI in hospitalized children in China.