Importance Atopic dermatitis (AD) is a common illness of childhood Objective The goal of this study was to evaluate the natural history of AD and determine the persistence of symptoms over time. Design A cross-sectional and cohort study. Setting A nation-wide long-term registry of children with AD. Participants Children enrolled in the Pediatric Eczema Elective Registry (PEER). Main outcome Self-reported outcome of whether or not a child’s skin was AD symptom-free for 6 months at 6 month intervals. Results 7,157 subjects were enrolled in the PEER study for a total of 22, 550 person-years. At least 2 years of follow-up was observed for 4,248 and at least 5 years of follow-up was observed for 2,416 children. Multiple demographic and exposure variables were associated with more persistent AD. At every age (i.e. 2 to 26 years), more than 80% of PEER subjects had symptoms of AD and/or were using medication to treat their AD. It was not until age 20 years that 50% of subjects had at least one lifetime six-month symptom and treatment free period. Conclusions and Relevance Based on this large longitudinal cohort study, symptoms associated with AD appear to persist well into the second decade of a child’s life and likely longer. AD is likely a life-long illness.