Objective To observe the effects of salmeterol / fluticasone combined with tiotropium in the treatment of sever to very sever COPD. Methods Eighty patients with severe to very severe stable COPD were recruited from outpatient of Central Hospital of Cangzhou between May 2008 and October 2009. The subjects were randomly divided into a salmeterol /fluticasone group and a combination group. The salmeterol / fluticasone group received salmeterol / fluticasone propionate, and the combination group received the combination therapy of tiotropium and salmeterol / fluticasone propionate. All patients had received the treatment for 12 months. At baseline and at the end of 1-month, 3-month, 6-month, 12-month, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the St. George’s Respiratory Questionnaire ( SGRQ) score were assessed. The number of exacerbations and the time to the first exacerbation were also recorded. Results At every visit, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the SGRQ score were improved in both groups compared with baseline ( Plt;0. 05) , especially in the combination group ( Plt;0.05) . Compared with the salmeterol /fluticason, the combination therapy with tiotropium significantly decreased the incidence of exacerbations and prolonged the time to the first exacerbation ( Plt;0.05) . And there was no significant difference between two groups in adverse effects ( Pgt;0.05) . Conclusions The combination therapy with salmeterol / fluticasone propionate and tiotropium was superior to salmeterol / fluticasone propionate in treatment of sever to very severe stable COPD patients in improving lung function, exercise tolerance, and quality of life, without additional adverse effects.