Objective: To determine the effect of anti-asthmatic inhalers salbutamol and budesonide on the surface microhardness of bovine tooth enamel. Materials and methods: The study was experimental, prospective, longitudinal, and comparative. The sample consisted of permanent mandibular incisors, which were prepared in (n = 90) blocks of dental enamel of size 3 × 3 mm and 2 mm thick, separated into 6 groups of 15 specimens each in sterile bottles properly labeled and contained in artificial saliva at 37°C. Three measurements (baseline, 5 days, and 10 days) were performed after immersion to determine the microhardness using a Vickers microdurometer programmed to apply a load of 100 gm for 15 seconds. Results: It was observed that the enamel surface microhardness decreased after 5 and 10 days, after being in contact with the anti-asthmatic inhalers based on salbutamol and budesonide. In addition, it was evidenced that there is a greater decrease in the superficial microhardness of the enamel when comparing the values at the beginning and after 10 days; likewise, the reduction in the microhardness of enamel exposed to budesonide was greater (120.8 kg/mm2) compared to salbutamol (112.3 kg/mm2) (p <0.001). Conclusion: The two anti-asthmatic inhalers studied decreased superficial enamel microhardness, with the budesonide-based inhaler having a greater erosive effect. Clinical significance: This research allowed us to know the values of the microhardness of the superficial enamel after being exposed to different anti-asthmatic inhalers that are indicated in daily clinical practice. Therefore, it is important to evaluate this microhardness since the use of different inhalers is very prevalent.