OBJECTIVES: To estimate the economic impact of the introduction of budesonide/formoterol fixed-dose combination (FDC) with a new inhaler, Spiromax®, focusing on an increment of medication compliance due to an enhancement of the inhalation technique for the treatment of Chronic Obstructive Pulmonary Disease (COPD) patients in five Spanish regions including Andalusia, Catalonia, Galicia, Madrid and Valencia. METHODS: A 4-year budget impact model was developed for the period 2015─2018 for patients with COPD from the Spanish Healthcare System perspective. Budesonide/formoterol FDCs delivered by Turbuhaler® and Spiromax® inhalers were considered. All inputs were obtained from the published literature: regional data on COPD prevalence, non-compliance rates due to a poor inhaler technique, healthcare utilization related to non-compliance, medical resources associated with COPD management, budesonide/formoterol adverse event rates, and resource utilization during hospitalization and at the emergency room. Based on the unit costs for drugs and medical resources, the annual treatment costs per patient associated to each inhaler and the annual cost per patient with an improvement in compliance were determined to estimate the overall budget impact. RESULTS: The population with moderate to severe COPD treated with budesonide/formoterol FDCs in 2015 was estimated at 19,514, 20,016, 7,778, 21,289 and 9,936 patients in Andalusia, Catalonia, Galicia, Madrid and Valencia, respectively. Annual mean cost per patient was €1,384 before the introduction of Spiromax® and €1,242 after its introduction and due to an improvement in medication compliance. Based on the forecast uptake of budesonide/formoterol FDC delivered by Spiromax®, the model estimated the budget savings at €2.34 million in Andalusia, €2.23 millions in Catalonia, €0.87 millions in Galicia, €2.23 million in Madrid and €0.77 million in Valencia, over the next four years. CONCLUSIONS: The introduction of budesonide/formoterol FDC delivered by Spiromax® for the treatment of moderate and severe COPD patients is likely to represent savings for all five regions.