OBJECTIVE： To observe clinical efficacy and safety of salmeterol fluticasone combined with tiotropium bromide in the treatment of COPD via different inhalation devices. METHODS： Eighty COPD patients were selected from our hospital during Jan. 2014 to Jan. 2015， and then divided into trial group and control group according to random number table， with 40 cases in each group. Both groups were given Salmeterol fluticasone inhalant 500 μg，bid+Tiotropium bromide inhalant 18 μg，qd. Control group was given medicine via inhalation device coming with medicine， while trial group was given medicine via gas compression type ultrasonic spray inhalator. Both groups were treated for 1 year. Blood concentration of medicine 0.5 h after medication， mMRC score and COPD acsessment test （CAT） score 3， 6， 9 months after treatment， the times of acute exacerbation during treatment， FEV1％ before and after treatment were all observed in 2 groups. The occurrence of ADR was recorded. RESULTS： Four cases withdrew from trial group and 1 case from control group. After medication， there was no statistical significance in blood concentration of fluticasone， salmeterol and tiotropium bromide between 2 groups （P＞0.05）. 0.5 h after medication， mMRC score of trial group was slightly lower than that of control group， without statistical significance （P＞0.05）； CAT score of it was significantly lower than that of control group， with statistical significance （P＜0.05）. The times of acute exacerbation in trial group during treatment was significantly less than control group， with statistical significance （P＜0.05）. The decrease of FEV1％ in trial group was slightly lower than control group， without statistical significance （P＞0.05）. The incidence of ADR in trial group was significantly lower than control group， with statistical significance （P＜0.05）. CONCLUSIONS： For COPD patients， salmeterol fluticasone combined with tiotropium bromide via gas compression type ultrasonic spray inhalator is better than inhalation device coming with medicine in clinical efficacy and safety.