BACKGROUND: Recent studies have reported the association between air pollution exposure and reduced kidney function. However, it is unclear whether air pollution is associated with an increased risk of acute kidney injury (AKI). OBJECTIVES: To address this gap in knowledge, we investigated the effect estimates of long-term exposures to fine particulate matter [PM ≤2:5 lm in aerodynamic diameter (PM2:5 )], nitrogen dioxide (NO2 ), and ozone (O3 ) on the risk of first hospital admission for AKI using nationwide Medicare data. METHODS: This nationwide population-based longitudinal cohort study included 61,300,754 beneficiaries enrolled in Medicare Part A fee-for-service (FFS) who were ≥65 years of age and resided in the continental United States from the years 2000 through 2016. We applied Cox-equivalent Poisson models to estimate the association between air pollution and first hospital admission for AKI. RESULTS: Exposure to PM2:5, NO2, and O3 was associated with increased risk for first hospital admission for AKI, with hazard ratios (HRs) of 1.17 (95% CI: 1.16, 1.19) for a 5-lg=m3 increase in PM2:5, 1.12 (95% CI: 1.11, 1.13) for a 10-ppb increase in NO2, and 1.03 (95% CI: 1.02, 1.04) for a 10-ppb increase in summer-period O3 (June to September). The associations persisted at annual exposures lower than the current National Ambient Air Quality Standard. DISCUSSION: This study found an association between exposures to air pollution and the risk of the first hospital admission with AKI, and this association persisted even at low concentrations of air pollution. Our findings provide beneficial implications for public health policies and air pollution guidelines to alleviate health care expenditures and the disease burden attributable to AKI. https://doi.org/10.1289/EHP10729.