The treatment of COPD (Chronic Obstructive Pulmonary Disease) aims to improve the patients's well-being and to reduce mortality, morbidity and the development of exacerbations. This study was thus designed to compare the efficacy and tolerability of salmeterol/fluticasone combination with tiotropium in patients with moderate COPD.This was an open, prospective, randomized trial in COPD patients whose FEV1 (forced expiratory volume in 1 second) levels were between 80% and 50% predicted. A total of 44 patients who met the inclusion and exlusion criteria and who gave written informed consent were included in the study. At the end of the two week wash-out period, the patients were randomized to receive either salmeterol 50 µg/fluticasone 500 µg combination as dry powder inhaler twice daily (SF Group) or tiotropium dry powder inhaler 18 µg once daily (T Group) for one year. These were equally distributed in the two groups (22 patients in each study group). At follow-up, the patients were required to come to the outpatient clinic at the third, sixth, ninth and twelfth months.There were no statistically significant difference between the two groups with regards to demographic features and baseline measurements. There were 1.2 ± 1.7 exacerbations in SF Group and 2.1 ± 2.2 exacerbations in T Group (p= 0.070). The time to the first exacerbation was 4.2 ± 4.0 and 4.2 ± 3.3 months, respectively (p= 0.697). The number of severe exacerbations that resulted in admission to the emergency department or hospital was 0.6 ± 1.0 and 1.1 ± 1.4, respectively (p= 0.245). Significant improvements were observed in CAT (CPOD Assessment Test) scores in both groups during the treatment period (p< 0.0001); but there was no difference between the two groups.This study has shown that in patients with moderate COPD, treatment with combined corticosteroid and long-acting beta-2 agonist provides similar improvements in pulmonary function tests, patient-reported outcomes and exercise capacity as compared a long-acting anticholinergics.