Inhaled corticosteroids (ICS) are one of the most commonly used asthma therapies and have highly variable treatment success. Polymorphisms in TBX21, a gene important for the biological action of corticosteroids, could be associated with treatment response in asthmatics. We genotyped for rs9910408 in TBX21 in 208 adult asthmatic patients, treated at least 3 years with ICS. Polymorphism rs9910408 was associated with response to ICS treatment. When treatment success was assessed by a decrease in bronchial hyperresponsiveness (BHR), the frequency of AA genotype was significantly higher in good responders (P = 0.049). This genotype related response was even more evident in the subgroups of non-smokers (P = 0.008) and in non-atopic patients (P = 0.009). AA genotype was overrepresented among good responders according to changes in FEV1 in the subgroups of non-smokers (P = 0.013) and in non-atopic patients (P = 0.048). Our results showed that treatment response to ICS, assessed as changes in BHR and FEV1, is associated with TBX21.