Background: Current evidence suggests that asthma patients with the ADRB2 Arg16 genotype have a poorer response to long-acting (2)-agonists (LABA), but the results remain inconsistent. Aim: This study assessed the association between Arg16 variants and treatment outcome in children treated with inhaled corticosteroids (ICS) and LABA. Materials & methods:ADRB2 Arg16 was genotyped in 597 children (4-12 years of age) participating in the PACMAN cohort study. A questionnaire was used to assess asthma control, frequency of asthma-related emergency department visits and use of oral corticosteroids in the past year. Results: Arg/Arg carriers with a reported use of ICS and LABA had an increased risk of oral corticosteroid use (odds ratio: 14.9; 95% CI: 1.59-140.1) and emergency department visits in the past year (odds ratio: 11.9; 95% CI: 1.22-115.8) compared to Gly/Gly carriers. This effect was not observed in Arg/Arg genotype carriers reporting ICS use only. Conclusion: Children who are homozygous for ADRB2 Arg16 have an increased risk of exacerbations when treated with combined LABA and ICS. Original submitted 4 September 2013; Revision submitted 27 September 2013