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Introduction: Worsening renal function during hospitalization for heart failure, defined as elevation in creatinine during admission, predicts adverse outcomes. Prior studies define worsening renal function using various creatinine elevations, but the relative value of definitions is unknown., Methods and Results: In a prospective cohort of 412 patients hospitalized for heart failure, we compared a spectrum of worsening renal function definitions (absolute creatinine elevations >/=0.1 to >/=0.5 mg/dL and 25% relative elevation from baseline) and associations with 6-month mortality, readmission, and functional decline. Creatinine elevation >/=0.1 mg/dL occurred in 75% of patients, and elevation >/=0.5 mg/dL occurred in 24% of patients. Risk of death rose with higher creatinine elevations (adjusted hazard ratio [HR] = 0.89, 1.19, 1.67, 1.91, and 2.90 for elevations >/=0.1 to >/=0.5 mg/dL). Maximum sensitivity of any definition for predicting mortality was 75% and maximum specificity was 79%. High creatinine elevation was a more important predictor of death than was a single measure of baseline creatinine., Conclusions: Larger creatinine elevations predict highest risk of death, yet even minor changes in renal function are associated with adverse outcomes. The choice of a "best definition" for worsening renal function has implications for the number of patients identified with this risk factor and the magnitude of risk for mortality.