The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups.Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose.