The objective of this study was to compare the cost-effectiveness of formoterol Turbuhaler, twice daily, versus salmeterol pMDI, twice daily, or salbutamol pMDI, as needed, in patients being regularly treated with inhaled corticosteroids. This clinical study was a prospective, 12-week, randomised, open parallel group comparison of the three bronchodilators in 362 patients (>18 years) with moderate to severe asthma. All patients were symptomatic on their current dose of inhaled corticosteroid. Total asthma-related costs were calculated as the sum of direct and indirect costs per patient per day. Direct costs consisted of the use of study-related medications, inhaled steroids, antibiotics, oral steroids, concomitant asthma medications, healthcare visits, emergency room visits, hospitalisations, out-of-pocket expenditures, and devices. Indirect costs consisted of missed work or usual activities due to asthma. Effectiveness was measured as the percentage of episode-free days, indicating the overall state of asthma control. The results revealed that total daily costs were significantly lower for formoterol compared with salmeterol (p<0.001), but no differences in effectiveness were seen. However, significant differences for both costs and effectiveness were found between the formoterol and salbutamol groups (p<0.001). Using the bootstrapping method, the cost per additional episode-free day associated with formoterol over salbutamol was estimated to be $2.48 CAD (95% confidence interval: -$4.09 to $8.65). Hence, when the incremental cost-effectiveness ratio was considered in the analysis, no significant difference in incremental total cost between the treatments could be detected. In conclusion, formoterol Turbuhaler, twice daily, is more cost-effective compared with twice daily salmeterol and as needed salbutamol in symptomatic patients with moderate to severe asthma.