OBJECTIVES Antibiotic exposure in children is a possible contributor to the increasing asthma prevalence in several countries. The present study aimed to investigate the association between antibiotic exposure and the risk of developing childhood asthma at 2-8 years of age. METHODS A case-control study was undertaken among children aged 2-8 years old between March and September 2010 in the Urmia district in the northwest of Iran. The cases were doctor-diagnosed asthmatic children based on Global Initiative for Asthma criteria (n=207), and the controls were children without respiratory symptoms (n=400) selected by frequency matching by age and gender. Clinical data including antibiotic exposure was collected by a validated and reliable questionnaire, which was completed by interviewing parents/guardians. RESULTS Antibiotic consumption during the first year of life increased the odds ratio [OR] of asthma symptoms at 2-8 years of age (crude OR, 2.26; 95% confidence interval [CI], 1.53-3.35; p<0.01), and the strength of association was similar after adjusting for a family history of asthma or atopic disorder, preterm delivery, birth order, and delivery method (adjusted OR, 1.91; 95% CI, 1.27-2.88; p=0.03). CONCLUSIONS Our study suggests that antibiotic consumption in children was associated with an increased risk of childhood asthma, and an additional confirmative study is needed.