OBJECTIVES: To assess 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 moderate to severe asthmatics 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 from the Spanish Healthcare System perspective. Budesonide/formoterol FDCs delivered by Turbuhaler® and Spiromax® were considered in this model. All inputs were obtained from the literature: regional data on asthma prevalence, non-compliance rates due to a poor inhaler technique, healthcare utilization related to non-compliance, medical resources associated with asthma 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 asthma treated with budesonide/formoterol FDCs in 2015 was estimated at 25,081, 12,392, 16,097, 17,829 and 15,148 patients in Andalusia, Catalonia, Galicia, Madrid and Valencia, respectively. Annual mean cost per patient was estimated at €1,619 before the introduction of Spiromax®, and at €1,481 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 €2.92 million in Andalusia, €1.35 million in Catalonia, €1.79 million in Galicia, €1.83 million in Madrid and 1.30 € million in Valencia, over the next four years. CONCLUSIONS: The introduction of budesonide/formoterol FDC delivered by Spiromax® for the treatment of moderate to severe asthma is likely to reduce the healthcare budget for five Spanish regions.