BACKGROUND: Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early-life exposure of a child to antibiotics increases the risk of early-onset AD. OBJECTIVES: We hypothesize that antibiotic exposure in utero or early in life (e.g. first 90 days) increases the likelihood that children develop AD. METHODS: Utilizing a large, prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The risk of AD in childhood was increased after in utero or early-life antibiotic exposure. For any in utero antibiotic exposure the HR (CI) was 1.38 (1.36-1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure [1.43 (1.41-1.44)] and for childhood exposure [1.81 (1.79-1.82)]. HRs were higher in children born to mothers without AD than in those with AD pointing to effect modification by maternal AD status. CONCLUSIONS: Children born to mothers exposed to antibiotics while in utero had, depending on the mother's history of AD, approximately a 20-40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early in life had a 40-80% increased risk of developing AD. Our study supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying the skin microbiome.