Introduction: The current study is to identify the performance of urinary tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for predicting renal replacement therapy (RRT) initiation and mortality in postoperative acute kidney injury (AKI) patients. Methods: Postoperative AKI patients were prospectively and consecutively enrolled. The biomarkers of urinary TIMP-2 and IGFBP7 were detected at the time AKI diagnosed (day 0) and 24 h later (day 1). The primary endpoint was the initiation of RRT, and the secondary endpoint was 30-day mortality. The receiver operating characteristic (ROC) curve was used to assess the performance of biomarkers for the prediction of RRT requirement. Results: There were 220 AKI patients enrolled in this study. Among the 220 patients, 33 (15.0%) initiated RRT during intensive care units period. Urinary (TIMP-2) × (IGFBP7), TIMP-2 and IGFBP7 on day 1 had fair performance for predict RRT initiation, the predictive area under the ROC curve (AUC) were 0.792 (0.732, 0.843), 0.784 (0.724, 0.837), and 0.770 (0.709, 0.824), respectively, with no significant difference. When they combined with clinically independent risk factors (nonrenal sequential organ failure assessment score, duration of surgery procedure, and serum creatinine at the time of AKI diagnosed) to construct predictive models for predicting RRT. The AUCs were greatly improved to be good. The best AUC was achieved by TIMP-2, which was 0.866 (0.814, 0.908). All of the biomarkers performed poor predictive values for predicting 30-day mortality. Conclusion: Urine concentrations of (TIMP-2) × (IGFBP7), TIMP-2 alone, and IGFBP7 alone on AKI day 1 show fair value for prediction of RRT initiation. However, they fail to predict 30-day mortality.