BACKGROUND: Acute kidney injury (AKI) is a clinical syndrome affecting almost one-fifth of hospitalized patients, as well as over half of the patients who are admitted to the intensive care unit (ICU). Stratifying AKI patients into groups based on severity and duration would facilitate targeted efforts for treating AKI. METHODS: In a retrospective, multicenter longitudinal cohort study of 2,187,254 hospital encounters from 935,679 patients who were admitted between 2012 and 2020 to health centers in the OneFlorida + Network, we analyzed the impact of AKI trajectories (i.e. rapidly reversed AKI, persistent AKI with renal recovery, and persistent AKI without renal recovery) on patients' clinical outcomes, including hospital, 30-day, 1-year, and 3-year mortality, kidney replacement therapy, new chronic kidney disease (CKD) within 90 days or 1-year of discharge, CKD progression within 1-year of discharge, resource utilization, hospital disposition, and major complications during hospitalization. RESULTS: Among all encounters, 14% of patients had AKI, of whom 63%, 21%, and 16% had Stage 1, 2, and 3, respectively, as the worst AKI stage. The fraction of patients with persistent AKI was 31%. Patients with AKI had worse clinical outcomes and increased resource utilization compared to patients without the condition. One-year mortality was 5 times greater for patients with persistent AKI compared to those without AKI. CONCLUSIONS: Persistent AKI was associated with prolonged hospitalization, increased ICU admission and greater mortality compared to the other groups. This may emphasize the critical need for devising strategies targeting effective management of AKI and prevention of persisting AKI.