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Introduction Preliminary results from the SABINA (SABA use IN Asthma) program showed lower overuse of short-acting β2-agonist (SABA) in Italy compared to other European countries. The aim of the present study was to ascertain whether SABINA’s results might have been affected by the Italian National Health System and pharmaceutical market dynamics, by examining patients’ characteristics in relation to SABA prescription/purchase habits. Methods Multiple approaches were used: (1) a retrospective study using the General Practitioners’ (GPs) Italian IQVIA Longitudinal Patient Database (LPD) to assess SABA overuse (more than two canisters/year) and its association with exacerbation risk; (2) a survey conducted across 200 Italian pharmacies to calculate the proportions of SABA purchases without a prescription; (3) a cross-sectional study on the specialists’ IQVIA Patient Analyzer database to understand the SABA prescription habits of specialists. Results Among SABA users identified through IQVIA LPD, the proportion of patients having more than two SABA canisters/year was 32%. Overall, patients prescribed more than two SABA canisters/year by GPs had 30% higher risk of exacerbations than patients with a maximum of two SABA canisters/year. The joint evaluation of IQVIA LPD and survey’s findings revealed that IQVIA LPD tracks three out of four SABA canisters dispensed. The survey showed that, on average, SABA users purchased four canisters/year. Patients prescribed SABA by specialists were more frequently men, younger, thinner, and had higher spirometry values. Conclusion SABA overuse is common in Italy, with a share of consumption not regulated by medical prescriptions. Because SABA overuse increases exacerbation risk, changes to national guidelines should be encouraged to ensure implementation of global recommendations. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01772-0.