The purpose of the study is to investigate the effectiveness of serum creatinine, the most common indicator of acute kidney injury (AKI), in predicting the prognosis of critically ill patients after cardiac surgery. Also, we sought to validate the use of this biomarker in assessing the direct outcome of a clinical setting. We selected 592 patients from our hospital; the relevant information including name, disease, gender, age, EuroSCORE, length of stay (LOS), days of mechanical ventilation, days of noninvasive positive pressure ventilation, days of continuous renal replacement treatment, and mortality was recorded. Creatinine of pre-operative, 24, and 48 h post-operation specimens were analyzed. The difference in serum creatinine levels at various time points was compared using t test. Spearman correlation was used to analyze the correlation of serum creatinine to AKI and hard outcomes. Receiver-operating characteristic curves were generated, and the areas under the curves (AUCs) were compared to validate the adequacy of creatinine in predicting the post-operative AKI. The 48 h post-operative and pre-operative serum creatinine were found to be informative in predicting the outcome of patients as indicated by the t test and Spearman correlation analysis. The 48 h creatinine with AUC of 0.811 was indicated to be significantly associated with the hard outcome. However, the 24 h and pre-operative creatinine with AUCs of 0.701 and 0.658, respectively, were not adequately related to the outcomes. In conclusion, contrary to the existing belief that creatinine is not an informative parameter for the diagnosis and prognosis of AKI, we found that when measured at 48 h of cardiac surgery, serum creatinine is reflective of the outcome.