Atopic dermatitis (AD) has been linked to systemic infections in adulthood, but large-scale studies are few and potential associations unclear.To examine whether adults with AD have increased risk of developing systemic infections leading to hospital-based management.Nationwide register-based cohort study including all Danish adults from 1995 through 2017. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox models.10,602 adults with AD (median age 29.8 years, interquartile range 22.6-44.8) and 106,020 reference individuals were included. The overall incidence rate per 10,000 person-years of systemic infections was 180.6 (95%CI 172.6-189.0) among AD adults compared with 120.4 (95%CI 118.3-122.5) among reference adults. The association between AD and systemic infections was observed for musculoskeletal (adjusted HR [aHR] 1.81, 95%CI 1.42-2.31), heart (aHR 1.75 95%CI 1.21-2.53), upper (aHR 1.42 95%CI 1.15-1.73) and lower respiratory tract infections (aHR 1.21 95%CI 1.10-1.33). The risk of sepsis (aHR 1.19 95%CI 1.01-1.44) and skin infections (aHR 2.30 95%CI 2.01-2.62) was also increased.The findings cannot be generalized to adults with milder AD seen outside the hospital system.We found an increased risk of systemic infections among adults with hospital managed AD.