This study investigated the therapeutic efficacy of two different β-blockers, metoprolol (β<sub>1</sub>-selective) and nipradilol (nonselective) for the treatment of idiopathic dilated cardiomyopathy (DCM). The New York Heart Association functional class improved in the metoprolol group (n = 9) and the nipradilol group (n = 9), but not in the control group who received conventional therapy (n = 8). The left ventricular ejection fraction increased in both the β-blocker groups (p < 0.01, p < 0.05). Lymphocyte β-adrenoceptors were upregulated in the nipradilol group (p < 0.01). Cardiac events were less common in both the β-blocker groups than in the control group (both p < 0.05). Thus, nipradilol improved symptoms and cardiac function with a favorable effect on sympathoneuronal activity as well as metoprolol in patients with DCM. Therefore, β<sub>1</sub>-selectivity is not essential to achieve therapeutic efficacy with β-blockade therapy for DCM.