Objectives To compare the rate, indications and type of antibiotic prescriptions in children with and without asthma. Design A retrospective cohort study. Setting Two population-based primary care databases: Integrated Primary Care Information database (IPCI; the Netherlands) and The Health Improvement Network (THIN; the UK). Participants Children aged 5-18 years were included from January 2000 to December 2014. A child was categorised as having asthma if there were ≥2 prescriptions of respiratory drugs in the year following a code for asthma. Children were labelled as non-asthmatic if no asthma code was recorded in the patient file. Main outcome measures Rate of antibiotic prescriptions, related indications and type of antibiotic drugs. Results The cohorts in IPCI and THIN consisted of 946 143 and 7 241 271 person years (PY), respectively. In both cohorts, antibiotic use was significantly higher in asthmatic children (IPCI: 197vs126 users/1000 PY, THIN: 374vs250 users/1000 PY). In children with asthma, part of antibiotic prescriptions were for an asthma exacerbation only (IPCI: 14%, THIN: 4%) and prescriptions were more often due to lower respiratory tract infections then in non-asthmatic children (IPCI: 18%vs13%, THIN: 21%vs12%). Drug type and quality indicators depended more on age, gender and database than on asthma status. Conclusions Use of antibiotics was higher in asthmatic children compared with non-asthmatic children. This was mostly due to diseases for which antibiotics are normally not indicated according to guidelines. Further awareness among physicians and patients is needed to minimise antibiotic overuse and limit antibiotic resistance.