BACKGROUND: Heart failure is a common and important cause of morbidity and mortality. Disease management offers promise in reducing the need for hospitalization and improving quality of life for heart failure patients, but experimental data on the efficacy of such programs are limited. METHODS AND RESULTS: A total of 151 patients hospitalized with heart failure were randomized to usual care or scheduled telephone calls by specially trained nurses promoting self-management and guideline-based therapy as prescribed by primary physicians. Nurses also screened patients for heart failure exacerbations, which they managed with supplemental diuretics or by contacting the primary physician for instructions. Outcomes included time to hospital encounter, mortality, number and cost of hospitalizations, functional status, and satisfaction with care. Intervention patients had a longer time to encounter (hazard ratio [HR] = 0.67; 95% confidence interval [CI] 0.47-0.96; P = .029), hospital readmission (HR = 0.67; CI 0.46-0.99; P = .045), and heart failure-specific readmission (HR = 0.62; CI 0.38-1.03; P = .063). The number of admissions, hospital days, and hospital costs were significantly lower during the first 6 months after intervention but not at 1 year. The intervention had little effect on functional status, mortality, and satisfaction with care. CONCLUSION: A nurse-administered, telephone-based disease management program delayed subsequent health care encounters, but had minimal impact on other outcomes.