Background and Objectives: By definition, acute kidney injury (AKI) is a clinical syndrome diagnosed when the increase in serum creatinine concentration is >0.3 mg/dL in 48 h or >1.5-fold in the last seven days or when diuresis < 0.5 mL/kg/h for a consecutive 6 h. AKI is one of the severe complications that may occur in the early postoperative period in patients undergoing heart valve surgery, significantly increasing the risk of death. Early implementation of renal replacement therapy increases the chances of improving treatment results in patients with postoperative AKI. The study assessed the predictive ability of selected preoperative and perioperative parameters for the occurrence of postoperative AKI requiring renal replacement therapy in the early postoperative period in a group of patients with severe valvular heart disease. Materials and Methods: A prospective study was conducted on a group of patients undergoing consecutive heart valve surgeries. The primary endpoint was postoperative AKI requiring renal replacement therapy. AKI was diagnosed with an increase in serum creatinine > 0.3 mg/dL in 48 h or >1.5-fold in the previous 7 days and/or a decrease in diuresis < 0.5 mL/kg/h for 6 h. The observation period was until the patient was discharged home or death occurred. Logistic regression analysis was used to assess which variables were predictive of primary endpoint, and odds ratios (OR) were calculated with a 95% confidence interval (CI). Multivariate analysis was based on the result of single factor logistic regression, i.e., to further steps, all statistically significant variables were taken into consideration. Results: A total of 607 patients were included in the study. The primary endpoint occurred in 50 patients. At multivariate analysis: NT-proBNP (OR 1.406; 95% CI 1.015-1.949; p = 0.04), CRP (OR 1.523; 95% CI 1.171-1.980; p = 0.001), EuroSCORE II (OR 1.090; 95% CI 1.014-1.172; p = 0.01), age (OR 1.037; 95% CI 1.001-1.075; p = 0.04) and if they stayed in the intensive care unit longer than 2 days (OR 9.077; 95% CI 2.026-40.663; p = 0.004) remained the independent predictors of the primary endpoint. The mean preoperative NT-proBNP level was 2063 pg/mL (±1751). Thirty-eight patients with AKI requiring renal replacement therapy died in intrahospital follow-up. Conclusions: The results of the presented study indicate that a high preoperative level of NT-proBNP and postoperative hemodynamic instability may be associated with a significant risk of a postoperative AKI requiring renal replacement therapy. The results of the study may also suggest that qualifying for heart valve surgery earlier may be associated with improved prognosis in this group of patients.