Renal dysfunction is a risk factor for morbidity and mortality in cardiac surgery patients. Serum Cystatin C (sCysC) is a well-recognized marker of early renal dysfunction but few reports evaluate its prognostic cardio-vascular role. The aim of the study is to consider the prognostic value of sCysC for cardiovascular mortality. Four hundred twenty-four cardiac-surgery patients (264 men and 160 women) were enrolled. At admission, all patients were tested for renal function and inflammatory status. Patients were subdivided in subgroups according to the values of the following variables: sCysC, serum Creatinine (sCrea), age, high sensitivity-C Reactive Protein, fibrinogen, surgical procedures and Kaplan-Meier cumulative survival curves were plotted. The primary end-point was cardiovascular mortality. In order to evaluate the simultaneous independent impact of all measured variables on survival we fitted a multivariate Cox-Proportional Hazard Model (CPHM). In Kaplan-Meier analysis 124 patients (29.4%) reached the end-point. In multivariate CPHM, the only significant predictors of mortality were sCysC (p<0.00001, risk ratio: 1.529, CI: 1.29-1.80) and age (p=0.039, risk ratio: 1.019, CI: 1.001-1.037). When replacing sCysC with sCrea, the only significant predictor of mortality was sCrea (p=0.0026; risk ratio 1.20; CI: 1.06-1.36). Increased levels of sCysC can be considered a useful biomarker of cardiovascular mortality in cardiac-surgery patients.