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ABSTRACT Background Although short-acting β2-agonist (SABA) overuse is associated with poor treatment outcomes, data on SABA use in the Middle East are lacking. Research design and methods In this cross-sectional study in patients (aged ≥12 years) with asthma, data on disease characteristics and asthma treatments were collected from the Middle Eastern cohort of the SABA use IN Asthma (SABINA) III study. Patients were classified by investigator-defined asthma severity and practice type. Multivariable regression models analyzed the association between SABA prescriptions and clinical outcomes. Results Of 1389 patients (mean age, 46.7 years; female, 69.5%), 85.7% had moderate-to-severe asthma and 88.7% were treated by specialists. Overall, 51.3% of patients experienced ≥1 severe asthma exacerbation in the previous 12 months, with 58.2% having partly controlled or uncontrolled asthma. Notably, 47.1% of patients were prescribed ≥3 SABA canisters (considered overprescription). SABA canisters were purchased over the counter by 15.3% of patients. Higher SABA prescriptions (vs 1–2 canisters), except 3–5 canisters, were associated with increased odds of uncontrolled asthma (p < 0.05). Conclusions SABA overprescription occurred in almost half of all patients in the Middle East, underscoring the need for healthcare providers and policymakers to adhere to the latest evidence-based recommendations to address this public health concern. Plain Language Summary Asthma is a long-term disease that causes inflammation of the airways in the lungs and affects both adults and children. Despite effective medicines, asthma remains poorly controlled in many patients. Inhaled steroids with anti-inflammatory properties are the most effective controller medications for asthma. However, many patients rely on rescue or reliever medications, including short-acting β2-agonists (SABAs), as they provide immediate relief from symptoms. However, SABAs do not treat the underlying inflammation of asthma and their continued overuse may place patients at risk of asthma attacks and hospitalization. The SABA use IN Asthma study, known as SABINA, examined SABA prescriptions in patients with asthma in 24 countries across five continents. As part of this study, data were collected on prescriptions for asthma medications (including SABA prescriptions) and the purchase of SABA over-the-counter (OTC) at the pharmacy without a prescription from 1389 patients aged at least 12 years across five countries in the Middle East (United Arab Emirates, Kuwait, Oman, Saudi Arabia, and Turkey). Nearly half of all patients were prescribed three or more SABA canisters in the previous 12 months, which is above that recommended by asthma treatment guidelines. SABA was also purchased OTC without a prescription by approximately 15% of patients, a majority of whom had already received a high number of SABA prescriptions. Prescription of six or more SABA canisters was associated with poor asthma control. Therefore, there is an urgent need for healthcare providers to follow the latest treatment guidelines for asthma to reduce SABA prescriptions. GRAPHICAL ABSTRACT