Background. To evaluate the possibility of predicting development of heart failure, we monitored left ventricular ejection fraction (LVEF) in addition to demographic data in patients with advanced breast cancer treated with epirubicin. Methods and Results. LVEF determination by radionuclide angiocardiography was performed serially before, during, and after treatment with 130 mg epirubicin/m2 every 3 weeks until disease progression or a cumulative dose of 1000 mg/m2 was reached (or heart failure occurred). Among 67 patients, heart failure developed in eight (12%). Age was 5 to 8 years greater and baseline LVEF was 7% less (95% confidence interval 3% to 13%) in patients who had heart failure than in the remaining patients. LVEF was slightly reduced in all patients during treatment. Three combined criteria, age ≤ 50 years, baseline LVEF ≤ 0.60, and decrease in LVEF to 0.50, had a positive predictive value of 70% (95% confidence interval 35% to 93%) and a negative predictive value of 98% (95% confidence interval 90% to 100%) with respect to development of heart failure. Conventional LVEF criteria were of less diagnostic value. Conclusions. Our results indicate that age and baseline LVEF determination mark a group of patients at high risk for development of epirubicin-induced heart failure. Monitoring of serial LVEF is indicated during treatment of these patients.