Objective: To explore the efficacy analysis of amiodarone and metoprolol in the treatment of patients with atrial fibrillation complicated with heart failure. Methods: 120 patients with atrial fibrillation complicated with heart failure who were hospitalized in the cardiology department of our hospital from January 2023 to June 2024 were selected as the research subjects. The patients were divided into the amiodarone group and the metoprolol group by the random number table method, with 60 cases in each group. The amiodarone group received amiodarone treatment; The metoprolol group was treated with metoprolol. The cardiac function [Left ventricular ejection fraction (LVEF), NYHA cardiac function classification], quality of life (Minnesota Heart Failure Quality of Life Questionnaire), incidence of major adverse cardiovascular events and occurrence of adverse reactions were analyzed and compared between the two groups. Results: After treatment, the LVEF of both groups was significantly increased compared with that before treatment, and the NYHA cardiac function classification was significantly decreased compared with that before treatment. Moreover, the improvement degrees of LVEF and NYHA cardiac function classification in the amiodarone group after treatment were significantly greater than those in the metoprolol group (P<0.05). After treatment, the quality of life scores of both groups were significantly lower than those before treatment (P<0.05), and the quality of life score of the amiodarone group was significantly higher than that of the metoprolol group (P<0.05). The total incidence of MACE in the amiodarone group was significantly lower than that in the metoprolol group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). Conclusion: For patients with atrial fibrillation complicated with heart failure, amiodarone is superior to metoprolol in terms of therapeutic effect in improving cardiac function, enhancing quality of life and reducing the incidence of MACE.