Objective To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients. Introduction Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function. Methods In this prospective study, urinary [TIMP-2]x[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]x[IGFBP7] > 0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2] x[IGFBP7] test. Results 107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l(2)/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]x[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001). Conclusions Urinary [TIMP-2]x[IGFBP7] test sufficiently detect patients with risk of AKI after major noncardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.