ABSTRACT. Acute renal failure increases risk of death after cardiac surgery. However, it is not known whether more subtle changes in renal function might have an impact on outcome. Thus, the association between small serum creatinine changes after surgery and mortality, independent of other established perioperative risk indicators, was analyzed. In a prospective cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery, the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox regression was used to correct for various established demographic preoperative risk indicators, intraoperative parameters, and postoperative complications. In the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in contrast to 8.9% in patients with increased postoperative serum creatinine values. Patients with large decreases (ΔCrea <−0.3 mg/dl) showed a progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum of −0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%]) was highest in patients in whom creatinine increased ≥0.5 mg/dl. For all groups, increases in mortality remained significant in multivariate analyses, including postoperative renal replacement therapy. After cardiac and thoracic aortic surgery, 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine. Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival.