Objectives: Cardio-renal syndrome type 1 (CRS1) complicates 40% of patients hospitalized for acute decompensated heart failure (ADHF) and is associated with poor prognosis. Factors associated with the development and recovery of CRS1 have not been completely understood, and the value of cystatin C in this context has not been studied. Materials and Methods: We evaluated the predictive value of cystatin C levels at admission and 24th hour and delta cystatin C (cystatin C change in the first 24 hours of admission) in the development and reversibility of CRS1 in patients hospitalized for ADHF. One hundred ten consecutive patients hospitalized for ADHF were enrolled. Results: Admission cystatin C [odds ratio (OR): 30.97, confidence interval (CI): 9.28-139.60, p<0.001], delta-cystatin C (OR: 41.26, CI: 7.75-93.55, p<0.001), furosemide dose given in first 24 hours of admission (OR: 1.941, CI: 1.541-4.112, p=0.009), and systolic pulmonary artery pressure (OR: 0.927, CI: 0.874-0.983, p=0.011) were independent predictors of CRS1. A ROC curve analysis showed that an admission cystatin C level at a cut-off point of 1.385 could detect AKI with 77.1% sensitivity and 77.4% specificity. Among 48 patients in the AKI group, renal function was recovered in 31 (64.6%). Delta-cystatin C (OR: 0.088, CI: 0.018-0.441, p=0.001), systolic pulmonary artery pressure (OR: 0.917, CI: 0.621-0.982, p=0.005), and furosemide dose given in first 24 h of admission (OR: 0.877, CI: 0.541-0.998, p=0.04) were independent predictors of recovery of renal function while admission creatinine and creatinine change in 24 hours were not. Conclusion: This study demonstrated the potential value of cystatin C and delta-cystatin C in CRS1. Further studies are required to determine the clinical utility of these findings.