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Recent reports suggest that β2-adrenergic receptor (ADRB2) genotypes are associated with therapeutic responses to β2 agonists in asthmatics. However, few studies have investigated therapeutic responses to β2 agonists in chronic obstructive pulmonary disease (COPD) patients. This study investigated immediate bronchodilator response and lung function responses following a 12-week treatment with a long-acting β2 agonist combined with a steroid inhaler in patients with COPD with various ADRB2 genotypes. One hundred four patients with chronic obstruction were genotyped for codon 16 and 27 polymorphisms of the ADRB2 gene. The immediate bronchodilator response to β2-agonist treatment was evaluated after inhalation of 400 μg salbutamol. In addition, long-term response was evaluated using observed change in spirometric values before and after the treatment with salmeterol (50 μg) combined with fluticasone propionate (500 μg) inhalation twice daily for 12 weeks. In terms of codon 16 variants, the immediate bronchodilator response to salbutamol was 6.4 ± 0.8% (% predicted value) in Arg/Arg patients, 4.9 ± 0.7% in Arg/Gly patients, and 5.8 ± 1.2% in Gly/Gly patients (p = 0.418). The FEV1 changes following the 12-week treatment were 7.0 ± 1.2% in Arg/Arg patients, 3.0 ± 1.5% in Arg/Gly patients, and 7.2 ± 1.2% in Gly/Gly patients (p = 0.229). Similarly, there was no difference between codon 27 variants in terms of immediate bronchodilator response or FEV1 changes after 12 weeks of treatment. We were unable to demonstrate an association between ADRB2 genotype and the effect on lung function of 12-week treatment with combined long-acting β2 agonist and glucocorticoid inhalation or on the immediate bronchodilator response to a short-acting β2 agonist in patients with COPD.