BACKGROUND Low cholesterol levels are associated with a worse outcome in patients with heart failure (HF). Use of statins in HF remains controversial. We aimed to assess whether the prognosis of patients with intrinsically low cholesterol levels differed from that of those with pharmacologically induced low cholesterol. Materials and METHODS We conducted a retrospective cohort study on 464 ambulatory patients attending a specialized HF clinic. Patients were cross-classified according to statin therapy and admission total cholesterol level (low cholesterol <150 mg/dL and cholesterol ≥150 mg/dL) (1) low total cholesterol level on statin therapy; (2) low total cholesterol level not taking statins; (3) cholesterol ≥150 mg/dL on statin therapy; and (4) cholesterol ≥150 mg/dL not on statin therapy. Patients were followed up to 5 years and the outcome was all-cause death. A Cox regression analysis was used in prognosis assessment. RESULTS Almost two thirds of the patients were men and the median population age was 69 years; 22.8% of the patients had preserved ejection fraction and 43.5% severe systolic dysfunction. The patients with an intrinsically low cholesterol had a hazard ratio of all-cause death up to 5 years of 2.38 (1.08-7.14) compared to those with low cholesterol induced by statin use. This association was independent of other variables associated with outcome. CONCLUSIONS Patients with HF with instrisically low cholesterol levels have a double risk of death up to 5 years compared to patients with pharmacologically induced low cholesterol. Clinicians should not limit the use of statins by fear of lowering the cholesterol levels.