OBJECTIVE To compare the clinical efficacy and safety of Fluticasone furoate/umeclidinium/vilanterol （FF/UMEC/VI） and Budesonide/glycopyrronium/formoterol （BUD/GLY/FOR） in the treatment of stable asthma-chronic obstructive pulmoary disease （COPD） overlap syndrome （ACOS）.METHODS A retrospective analysis was performed on clinical data of 157 patients with stable ACOS who received standardized treatment at the Affiliated Hospital of Xuzhou Medical University from March 2023 to March 2025. Patients were assigned to the FF/UMEC/VI group （ n＝ 80， receiving FF/UMEC/VI in addition to baseline therapy） and the BUD/GLY/FOR group （ n＝ 77， receiving BUD/GLY/FOR in addition to baseline therapy） according to the treatment regimens. The lung function parameters [forced expiratory volume in one second （FEV 1 ）， forced vital capacity （FVC）， FEV 1 /FVC， FEV 1 percentage of predicted value （FEV 1 %pred）， peak expiratory flow （PEF）]， inflammatory markers [peripheral blood eosinophils （EOS） count， fractional exhaled nitric oxide （FeNO） level， serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）]， and clinical symptom assessment indicators [Asthma Control Test （ACT） scores， COPD Assessment Test （CAT） scores， modified Medical Research Council Dyspnea Scale （mMRC） grades] were compared between the two groups at baseline， week 12 and week 24. The occurrences of acute exacerbations and adverse reactions during the 24-week treatment were documented.RESULTS At baseline， there were no statistically significant differences in lung function parameters， inflammatory markers， or clinical symptom assessment indicators between the two groups （ P ＞0.05）. At weeks 12 and 24， all the above indicators in both groups were significantly improved compared with pre-treatment values in the same group （ P ＜0.05）. The FF/UMEC/VI group showed significantly greater improvements in FEV 1 ， FEV 1 %pred and PEF at week 24， as well as IL-6 and TNF-α levels， ACT and CAT scores， and mMRC grades at both weeks 12 and 24， than the BUD/GLY/FOR group at the corresponding time points （ P ＜0.05）. Within the 24-week treatment， the incidence and frequency of acute exacerbations in the FF/UMEC/VI group were significantly lower than those in the BUD/GLY/FOR group （ P ＜0.05）. There was no statistically significant difference in the incidence of adverse reactions between the two groups （ P ＞0.05）.CONCLUSIONS Both FF/UMEC/VI and BUD/GLY/FOR can effectively improve lung function， reduce inflammation， and alleviate symptoms in patients with ACOS， and both demonstrate good safety profiles； FF/UMEC/VI shows more pronounced advantages in improving long-term lung function， reducing levels of systemic inflammatory markers， and preventing and controlling acute exacerbations， making it more suitable for the long-term management of patients with ACOS in the stable phase.