Background and Objective: Acute kidney injury (AKI) remains a serious health condition around the world, and is related to high morbidity, mortality, longer hospitalization duration and worse long-term outcomes. The aim of our study was to estimate the significant related factors for poor outcomes of patients with severe AKI requiring renal replacement therapy (RRT). Materials and Methods: We retrospectively analyzed data from patients (n = 573) with severe AKI requiring RRT within a 5-year period and analyzed the outcomes on discharge from the hospital. We also compared the clinical data of the surviving and non-surviving patients and examined possible related factors for poor patient outcomes. Logistic regression was used to analyze the odds ratio for patient mortality and its related factors. Results: In 32.5% (n = 186) of the patients, the renal function improved and RRT was stopped, 51.7% (n = 296) of the patients died, and 15.9% (n = 91) of the patients remained dialysis-dependent on the day of discharge from the hospital. During the period of 5 years, the outcomes of the investigated patients did not change statistically significantly. Administration of vasopressors, aminoglycosides, sepsis, pulmonary edema, oliguria, artificial pulmonary ventilation (APV), patient age ≥ 65 y, renal cause of AKI, AKI after cardiac surgery, a combination of two or more RRT methods, dysfunction of three or more organs, systolic blood pressure (BP) ≤ 120 mmHg, diastolic BP ≤ 65 mmHg, and Sequential Organ Failure Assessment (SOFA) score on the day of the first RRT procedure ≥ 7.5 were related factors for lethal patient outcome. Conclusions: The mortality rate among patients with severe AKI requiring RRT is very high—52%. Patient death was significantly predicted by the causes of AKI (sepsis, cardiac surgery), clinical course (oliguria, pulmonary edema, hypotension, acidosis, lesion of other organs) and the need for a continuous renal replacement therapy.