Background: Atopic dermatitis (AD) is associated with increased systemic inflammation and cardiovascular risk. Although previous studies have found increased inflammatory proteins in the blood of patients with AD, detailed comparison among patients with AD of different ages is unavailable. Objective: To characterize the blood proteomic signature of patients with AD as a function of age. Methods: We used the OLINK high-throughput proteomic assay to measure serum inflammatory and cardiovascular risk proteins in 71 patients with moderate to severe AD from 3 age groups (18-40 years old [n = 26], 41-60 years old [n = 24], and >60 years old [n = 21]) compared with 37 age-matched controls. Total and allergen-specific serum IgEs were also measured. Results: When we compared patients with AD from 3 different age groups with their respective controls, we identified a total of 172 differentially expressed proteins. TH2 chemokines (CCL13, CCL17) were consistently elevated in patients with AD across all ages (P < .05), whereas TH1 (CXCL10) and TH17 (KYNU, CCL20) markers incrementally increased with age in both patients with AD and healthy subjects. Elderly patients with AD (>60 years old) exhibited striking upregulation of key proinflammatory proteins, including markers of atherosclerosis (CCL4, CCL7, SORT1), cardiovascular risk (GDF15, MPO, ST2), cell adhesion (CDH3), and apoptosis (FAS; all P < .05) compared with younger patients with AD and age-matched controls. We also found that total and allergen-specific serum IgEs decreased significantly with age in patients with AD (P < .05). Conclusion: Elderly patients with AD had increased levels of systemic inflammatory markers, including those associated with cardiovascular and atherosclerosis risk, which may explain their increased incidence of cardiovascular disease. This finding suggests that older patients with AD may benefit from cardiovascular disease screening and prevention.