Abstract Objective: To assess the characteristics of total immunoglobulin E (IgE) and allergen-specific IgE (sIgE) to 20 common allergens in 154 patients with atopic dermatitis (AD). To assess the correlation of clinical food allergy with positive food allergens’ sIgE results. We further discuss the significance of IgE as a potential biomarker for AD disease severity. Methods: A total of 154 AD patients were collected from 15 hospitals nationwide in China from 2019 to 2021. Serum IgE was measured using reverse-enzyme immuno capture test (REAST). Patients were required to have at least one positive sIgE (N ≥ 0.35 IU/mL). Patients were divided into groups according to gender, age, disease severity, and region. SPSS 26.0 software was used for statistical analysis. Results: Compared with adolescent and adult, AD in infancy and childhood showed significantly higher frequencies of positive sIgE to food allergens, including egg, cow milk, and wheat (P < 0.01). However, adolescent and adult AD showed significantly higher frequencies of positive sIgE to inhaled allergens, dermatophagoides farinae, and house dust mite. In addition, sIgE in different sexes were different. Compared with women, men showed higher frequencies of positive allergen-specific IgE level to wheat, dermatophagoides farinae, and house dust mite. The most common food allergens with elevated sIgE levels were egg (71%), cow milk (39%) and wheat (32%). However, AD patients reported seafood, including crab, shrimp, and fish, as the most frequent food allergens which aggravate their disease in their daily life. Only 18 (12%) patients reported definite correlation of clinical practice with positive food allergens’ IgE results. Among 154 sIgE-positive patients, 99 patients had an increase of total IgE (≥60 IU/ml). TotalIgE (tIgE) levels were significantly different between mild (193 ± 239 IU/mL), moderate (170 ± 202 IU/mL), and severe (375 ± 343 IU/mL) forms of AD patients (P < 0.01). AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms (280 ± 286 IU/mL vs 194 ± 248 IU/mL). Conclusion: Neither sIgE nor tIgE levels can be used to evaluate the condition or severity of AD. AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms. Infantile AD patients are more allergic to food, while adolescents and adults are more allergic to environmental antigens. IgE tests must be interpreted by combining with clinical history to avoid unnecessary food avoidance. Early food allergen introduction for infants may be promising for the prevention of food allergies.