Purpose: Magnesium sulfate (MgSO4) emerged as an adjunctive therapy to help manage acute severe asthma refractory to the first-line therapy, such as oxygen, ipratropium, corticosteroids, and bronchodilators. Despite the known benefits of MgSO4, limited information is available regarding potential adverse effects (AEs). We aimed to investigate potential AEs and clinical response of intravenous MgSO4 by assessing vital signs and the modified Wood-Downes score (mWDS), a relevant clinical scoring system. Methods: This investigation constitutes a prospective, single-arm study, conducted from June 2022 through May 2023, in a pediatric emergency department of the quaternary public hospital in Brazil. This study included all children aged 3-14 years who visited the pediatric emergency department during the period and underwent a 6-hour continuous infusion of MgSO4 at 50 mg/kg/hour, against acute severe asthma, a case refractory to the first-line therapies. We evaluated the safety and efficacy of the infusion by using vital signs and the mWDS. Clinical response was defined as a reduction of at least 1 point in the scoring system.Results: We analyzed a total of 42 children including 24 boys (57.1%), whose mean age was 5.7 ± 2.4 years. The 6-hour continuous infusion of MgSO4 reduced mWDS from 3 (interquartile range, 3-4) to 2 (2-3) (P < 0.001) and resulted in the clinical response in 30 children (71.4%) without an AE. After the infusion, 13 of the 15 children (86.7%) classified as having moderate asthma exacerbation (mWDS, 4-6) were improved to having mild asthma exacerbation (mWDS, 1-3) (P < 0.001). The mean serum magnesium concentration after the infusion was 4.7 mg/dL. Pneumonia and viral infection did not predict the clinical response.Conclusion: This study indicates the safety and efficacy of the 6-hour continuous infusion of MgSO4 as a therapeutic option for acute severe asthma, which is refractory to the first-line therapy.