Background Amiodarone, which is an antiarrhythmic drug used to treat life-threatening arrhythmias, is effective in patients with chronic heart failure. However, its effectiveness compared with β-blockers has not yet been reported. Methods and results In 30 patients (mean age, 57 ± 13 years) with dilated cardiomyopathy, we compared 15 patients receiving amiodarone (group A) with 15 patients receiving metoprolol (group B). Before and after 1 year of treatment, cardiac iodine 123 metaiodobenzylguanidine uptake was assessed from the total defect score, heart-to-mediastinum activity ratio based on delayed images, and washout rate. New York Heart Association class and echocardiographic left ventricular ejection fraction were also assessed. In both groups the total defect score decreased (from 25 ± 11 to 16 ± 10 in group A, P < .01; from 26 ± 10 to 18 ± 11 in group B, P < .01), the heart-to-mediastinum activity ratio increased (from 1.63 ± 0.16 to 1.81 ± 0.29 in group A, P < .01; from 1.63 ± 0.21 to 1.85 ± 0.3 in group B, P < .01), and the washout rate decreased (from 51% ± 12% to 38% ± 14% in group A, P < .01; from 48% ± 11% to 37% ± 8% in group B, P < .01). Left ventricular ejection fraction increased (from 30% ± 9% to 42% ± 11% in group A, P < .01; from 26% ± 7% to 46% ± 16% in group B, P < .01) and New York Heart Association functional class improved (from 3.1 ± 0.5 to 1.8 ± 0.7 in group A, P < .01; from 2.9 ± 0.5 to 1.7 ± 0.6 in group B, P < .01). Conclusion Amiodarone treatment can improve cardiac symptom, function, and sympathetic nerve activity, as evaluated by I-123 metaiodobenzylguanidine imaging in patients with dilated cardiomyopathy, which improves to a similar extent with β-blocker treatment.