Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF).A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238–370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min −1 1.73 m −2 . After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively).In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min −1 1.73 m −2 , and both CKD-EPI equations improved clinical risk stratification.