Hypercholesterolemia is a risk factor for development of coronary artery disease (CAD), however, several reports have suggested that low serum cholesterol is associated with a worse prognosis in patients with congestive heart failure (CHF). The objective of this study was to determine the prognostic value of cholesterol for CHF. The study subjects consisted of 133 consecutive patients hospitalized in our institution for progressive heart failure from April 2000 to March 2003. Thirty-two percent of the patients had CAD. After improvement of congestive heart failure and discharge from the hospital, lipid profiles, including serum total cholesterol (TC), triglycerides, and high and low density lipoprotein cholesterol (HDL, LDL, respectively), were obtained. During the follow-up period (2.3 +/- 0.9 years), 21 patients died. There was a significant difference between survivors and nonsurvivors in HDL (53 +/- 15, 43 +/- 15 mg/dL, P = 0.01), but no differences were observed in other variables. In patients with CAD, survivors had significantly lower TC concentrations (179 +/- 30 versus 246 +/- 55 mg/dL, P = 0.004), although in patients without CAD, survivors had significantly higher TC concentrations (203 +/- 37 versus 170 +/- 40 mg/dL, P = 0.02). Multivariate analysis showed high TC predicted a worse outcome in patients with CAD (odds ratio (OR) = 1.052, 95% confidence interval (CI) 1.002-1.104, P = 0.04), but a better outcome in patients without CAD (OR = 0.972, 95% CI 0.948-0.997, P = 0.03), independent of age, gender, medication, and complications. Thus, low serum cholesterol is associated with an improved outcome in patients with CAD, while it predicts a worse outcome in patients without CAD.