Heart failure (HF) is a public health problem with ever-growing costs. Signs such as jugular venous pressure and third heart sound have been associated with disease prognosis. Symptoms of heart failure are frequently subjective, and their real value is often overlooked. The authors aimed to assess the relationship between orthopnea and left ventricular ejection fraction (LVEF) and hospitalization rate in patients referred to the HF clinic. One hundred fifty-three new consecutive patients referred to the HF clinic from September 2001 to July 2002 were reviewed. Information about orthopnea was available at baseline and at a 6-month to 1-year follow-up. One hundred thirty-one patients had a baseline multigated radionuclide ventriculogram scan, and 68 patients had a follow-up multigated radionuclide ventriculogram scan available. The patients were divided into groups by presence of orthopnea and compared with respect to LVEF and hospitalization rate. Patients with or without orthopnea had similar LVEFs at baseline (32%+/-17% vs. 33%+/-15%, respectively; p=NS). However, patients who were orthopnea-free at the follow-up visit had a significant LVEF improvement whereas patients with ongoing orthopnea at follow-up had no LVEF improvement (11%+/-13% vs. -1%+/-6%; p<0.001). Patients who presented with persistent orthopnea had a significantly higher rate of hospitalization (64% vs. 15.3%; p=0.0001). Persistent orthopnea in HF patients is associated with a significantly higher rate of hospitalization and with worsening or no improvement in LVEF. Patients with persistent orthopnea may require a more aggressive approach to improve their outcome. This result may help centers with limited access to LVEF measurements to better stratify HF patients' risk.