Background In critical care patients, the diagnosis of subclinical acute kidney injury (AKI) might be difficult with measurements of serum creatinine and estimated glomerular filtration rate (eGFR). Their 'sensitive kidneys' can easily be affected from sepsis, underlying diseases, medications and volume status and if they can be detected earlier, some preventive measures might be taken. In this study we aimed to determine whether admission serum cystatin C (sCys-C) and other clinical parameters can identify subclinical AKI in medical intensive care unit (ICU) patients with normal creatinine-based eGFR at admission. Methods A prospective cohort study, performed in an adult ICU of a university hospital between January 2008 and March 2013. The blood samples were obtained within the first 24-48 hours of admission and sCys-C levels were analyzed with particle-enhanced immunonephelometric assay. AKI development was assessed according to RIFLE criteria. The cutoff value of sCys-C for the prediction of AKI was determined with receiver operating characteristic (ROC) curve analysis. Results A total of 72 patients were included in the study and 19 (26%) of them developed AKI. Among the patients with AKI admission sCys-C levels were significantly higher when compared with non-AKI patients (1.06 +/- 0.29 vs. 0.89 +/- 0.28 respectively, p = 0.026). With ROC curve analysis, the threshold level for sCys-C was 0.94 mg/L with 63% sensitivity and 66% specificity [AUC: 0.67, p = 0.026]. With logistic regression analysis 'high sCys-C levels at admission' (OR = 4.73; 95%CI 1.03-21.5, p = 0.044) was found as one of the independent variables for the prediction of AKI development, in addition to 'being intubated before ICU admission' (OR = 10.2; 95%CI 1.72-60.4, p = 0.01) and 'hypotension during ICU follow-up' (OR = 12.3; 95%CI 2.5-60.1, p = 0.002). Conclusion In this cohort of patients, a high sCys-C level at admission was found to be a predictor of subclinical AKI arising during their ICU stay. If supported with further studies, it might be used to provide more accurate and earlier knowledge about renal dysfunction and to take appropriate preventive measures.