Objective: To explore the influence of salmeterol fluticasone plus tiotropium bromide and low dosage prednisone plus aminophylline on cardiac function in patients with chronic obstructive pulmonary disease (COPD) combined with chronic cor pulmonale. Methods: A total of 111 cases of COPD with chronic cor pulmonale patients in the stationary stage were recruited as subjects and randomly divided into three groups with 37 cases in each. Three groups received same routine treatment (diuretic drug, vasolidator, cardiac stimulant). The control group solely received routine treatment. The inhalation group had additional therapies of sameterol fluticasone (50/500 μg) twice daily plus tiotropium bromide once per day. The oral drug group had additional therapies of prednisone 5 mg once per day plus slow release aminophylline 100 mg twice per day based on the routine treatment. The right ventricular outflow tract, right ventricular internal diameter, right pulmonary artery trunk, pulmonary artery pressure, left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) in the three groups were measured and compared before and after 48 weeks of treatment, as well as the fasting blood glucose, plasma cortisol and lumbar spine bone mineral density in these three groups. Results: After treatment, all of the cardiac function indexes in patients of the inhalation group and the oral drug group were improved compared to those before treatment (P < 0.05) and those of the control group (P < 0.05). There were no significant differences existed in the pulmonary artery pressure of the inhalation group and oral drug group after treatment (P > 0.05). However, the right ventricular outflow tract, right ventricular internal diameter, right pulmonary artery trunk, LVEF and BNP in the inhalation group were more significantly improved than those in the oral drug group (P < 0.05). There were no significant differences among the fasting blood glucose, plasma cortisol and lumbar spine bone mineral density of these three groups before and after treatment (P > 0.05), and the levels of plasma cortisol in the three groups were all in normal level before and after treatment. Conclusion: Both of salmeterol fluticasone plus tiotropium bromide and low dosage prednisone plus aminophylline improve cardiac function in patients with chronic obstructive pulmonary disease combined with chronic cor pulmonale, and the former seems better.