The study retrospectively followed 560 patients undergoing open heart surgery and evaluated the impact of preoperative changes in serum creatinine (ΔScr) on the development of acute kidney injury (AKI) and hospitalization outcomes. AKI developed after surgery in 40.2% of patients. Increasing ΔScr was associated with an increased risk of AKI (adjusted odds ratio [AOR] 1.51 per 0.1 mg/dL increase; 95% CI 1.32–1.72), severe AKI (AOR 1.45; 95% CI 1.24–1.70), and AKI without recovery (AOR 1.37; 95% CI 1.19–1.59). Patients with negative ΔScr who developed AKI had higher in-hospital mortality and longer ICU stay (>72 hours) than patients without AKI. Negative ΔScr was independently associated with higher in-hospital mortality (AOR 4.50; 95% CI 1.00–20.15) and longer ICU stay (AOR 2.81; 95% CI 1.13–6.96) compared with normal ΔScr. With increased ΔScr, no such significant associations with mortality or length of stay in the ICU were found. In patients without AKI, neither a negative nor an increased change in preoperative creatinine was associated with higher mortality or longer ICU stay.