Early-life antibiotic use is associated with allergic diseases. The risk factors for the progression from atopic dermatitis (AD) to asthma or allergic rhinitis are still unknown. We aimed to investigate the association between exposure to different antibiotics and the risk of new-onset asthma in children with AD. By using the Longitudinal Health Insurance Database 2005, we selected AD patients less than 6 years old identified by ICD-9-CM code 691.8. The case group was defined as those having new-onset asthma, and the control group was defined as those without an asthma history. Information on antibiotic exposure in the 5 years prior to the index date was collected from drug prescription records. We estimated the adjusted odds ratio by using conditional logistic regression, adjusted for age, sex, index year, other potential risk factors and antibiotics. Antibiotic exposure was associated with the development of asthma in patients with AD (aOR = 3.68, 95% CI 2.13-6.36), particularly for patients less than 5 years old (aOR = 4.14, 95% CI 2.24-7.64) (p for trend < 0.001), even though lower cumulative antibiotic defined daily doses (DDDs) were associated with new-onset asthma occurrence. Antibiotic exposure, especially macrolide exposure, is associated with an increased risk of asthma in patients with AD.