Introduction: Acute heart failure (AHF) is a life-threatening disease with a high mortality rate. Cardio-renal syndrome (CRS) has received much attention because of its relation to the poor prognosis of hospitalized patients. In both acute and chronic cardiac disease, kidney impairment is a significant predictor of outcome. Finding a more sensitive renal damage marker is a top priority due to the disadvantage of the existing marker creatinine. Several new acute kidney injury (AKI) biomarkers are being studied. Cystatin Cis a kidney function biomarker that has also been investigated for its use in acute kidney injury early detection. Aim: was to assess the outcome of using cystatin C as a new AKI biomarker in patients diagnosed with AHF and its effect on hospital stay and in-hospital mortality. Methods: Cystatin C levels were measured on admission and 48 hours later in 200 hospitalized AHF patients. The amount of increase in cystatin C after 48 hours was measured, as well as the impact of a cystatin C increase on the hospital course. Results: The mean population age was 66.4 years old, while 49% of the population were females. AKI was detected in 16% of patients with >0.3 mg/L rise in cystatin C within two days of hospital admission, and this led to 3 days (P = 0.01) significant more extended hospital stay while in-hospital mortality was more but could not reach statistical significance (P = 0.239). Conclusion: In patients with acute heart failure, elevation in Cystatin C within 48 hours of hospital admission is a good detector of early acute kidney injury and has a detrimental impact on their hospital course.