Studies on the prevalence of atopic dermatitis (AD) in adults in general populations are scarce worldwide. We performed a retrospective population-based observational cohort study of 537 098 adult patients diagnosed with AD in Catalonia, Spain, a larger population than in previous studies. Objectives: To study the prevalence of AD by age, sex, disease severity, multimorbidity, serum total immunoglobin E (tIgE), and appropriate medical treatment (AMT) for the population of Catalonia. The study population comprised adult individuals (≥18 years) diagnosed with AD according to medical records at different health care levels (primary, hospital, emergency) in the Catalan Health System. Statistical analyses were conducted to evaluate sociodemographic characteristics, prevalence, multimorbidity, serum tIgE, and AMT. The prevalence of AD in the adult Catalan population was 8.7%, being higher for nonsevere disease (8.5%) than for severe disease (0.2%) and in females (10.1%) than in males (7.3%). Topical corticosteroids were the most prescribed drug (66.5%), and treatment was prescribed more frequently in severe AD patients, especially systemic corticosteroids (63.8%) and immunosuppressants (60.7%). More than half of severe AD patients (52.2%) had serum tIgE ≥100 kU/L, and higher values were observed for those with multimorbidity. The most frequent comorbid respiratory diseases were acute bronchitis (13.7%), allergic rhinitis (12.1%), and asthma (8.6%). We provide new and robust evidence of the prevalence of AD and related characteristics in adults using a large-scale population-based study and a more significant cohort of individuals.