OBJECTIVES: The safety, effectiveness and indications for ultrafiltration (UF) are not well established. We hypothesized that UF would not worsen renal function in patients with heart failure (HF) who were not responding to medical therapy. METHODS: Data was collected for patients who underwent UF between 2006 and 2010 (n = 72, median age 61 years, 54% males, 61% Caucasian, 54% left ventricular ejection fraction ≥ 40%). RESULTS: Baseline GFR was 38 ml/min/1.73 m2. All patients were initially treated with loop diuretics and 58% required a thiazide-like diuretic or vasoactive agent. UF resulted in total fluid removal of 11.3 liters and weight loss was 9.7 kg. The median decrease in eGFR during UF was 4.5 ml/min/m2 (IQR--13, 0; p < 0.01) and 43% of patients experienced a ≥ 20% decrease in eGFR. Ten percent of patients required dialysis and 13% died, received a ventricular assist device/cardiac transplant or were discharged to hospice. CONCLUSIONS: In a cohort of HF patients who did not respond to medical therapy, UF was associated not only with a significant reduction of body weight and fluid removal, but also acute worsening of renal function. Further research to identify the appropriate population for UF, long-term outcomes and the intensity of treatment is required if UF is to gain wide acceptance for HF management.