Objective: To explore the clinical effect of bisoprolol combined with digoxin in the treatment of elderly patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF). Methods: A total of 70 elderly patients with CHF complicated with persistent AF were selected and randomly divided into control group (conventional drug combined with digoxin, n=35) and experimental group (bisoprolol on the basis of control group, n=35). The maximum, minimum and average ventricular rate as well as cardiac function indexes [left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD)] were compared between the two groups before and after treatment. Results: After treatment, the maximum, minimum and average ventricular rates, LVEDD and LVESD of elderly CHF patients with persistent AF in control group and experimental group were significantly decreased (P<0.05) while LVEF was significantly increased (P<0.05). The maximum, minimum and average ventricular rates, LVEDD and LVESD of elderly CHF patients with persistent AF were obviously lower (P<0.05) while the LVEF was significantly higher in experimental group (P<0.05). During treatment, no statistical significance was found in the incidence of adverse reactions between groups (P>0.05). Conclusion: Bisoprolol combined with digoxin can effectively regulate the ventricular rate and improve cardiac function in elderly CHF patients with persistent AF, without increasing the occurrence risk of adverse reactions.