Background Many studies have shown a one-time I-123-metaiodobenzylguanidine (MIBG) scan during a stable period to be useful for determining the prognosis of patients with chronic heart failure (CHF). However, we recently reported that the delta washout rate (WR) determined from serial I-123-MIBG scintigraphic studies is the best prognostic value in patients with CHF. Methods A total of 208 patients with CHF (left ventricular ejection fraction <45%), but no cardiac events for at least 5 months, were identified on the basis of a history of decompensated acute heart failure requiring hospitalization. The patients underwent I-123-MIBG scintigraphy and echocardiography just before leaving the hospital and after 6 months of treatment. We evaluated two models for predicting cardiac death using the Cox proportional hazards regression analysis. In addition to clinical characteristics, New York Heart Association functional class and pharmacotherapy, one model included variables of baseline scintigraphic and echocardiographic parameters (model A), and the other model included those of delta (i.e. follow-up minus baseline) scintigraphic and echocardiographic parameters (model B). Results Of the 208 patients, 56 experienced fatal cardiac events during the study. In model A, a Cox proportional hazards analysis showed baseline WR >= 50% to be the only independent predictor of cardiac death (hazard ratio = 2.335, 95% confidence interval = 1.142-4.774, P = 0.020). In model B, delta-WRZ >= -5% was the only incremental predictor of cardiac death (hazard ratio = 4.444, 95% confidence interval = 1.511-13.069, P = 0.009). The survival rates of patients with a delta-WR of less than -5% were significantly higher for those with a baseline WR of less than 50% (P = 0.036). Moreover, high delta-WR was the best predictor compared with single scan, single echocardiography, and their combination evaluated by the global v 2 analysis. Conclusion Baseline WR and delta-WR obtained from I-123-MIBG scintigraphy can be used as independent predictors of cardiac death, and two I-123-MIBG scintigraphic studies are more useful than a one-time scan in stabilized patients with CHF. Nucl Med Commun 31: 807-813 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.