Abstract: This article investigates the performance of special knitwear made and recommended for sufferers of atopic dermatitis. Atopic dermatitis is a condition that causes dry, itchy and inflamed skin. Generally, fabrics with hygienic, antimicrobial, and mechanical non-irritating properties are recommended for sufferers from atopic dermatitis. The idea is to find the optimal textile structure that eliminates pain and wearing discomfort (both sensorial and thermo-physiological components). Based on a questionnaire survey of the needs of people with dermatitis, a group of properties was determined that crucially influence total wearing comfort. The measurement of these properties was conducted on eight commercially used knitwear types. Sensorial comfort was represented by parameters of total hand value, subjective wearing value, and warm/cold feeling value; physiological comfort by thermal conductivity, moisture management, water vapor and air permeability, and drying efficiency. The decision-making method Technique for Order of Preference by Similarity to Ideal Solution was used to determine the best solution considering the combination of the properties mentioned above. In summary, high air and water vapor permeability, hand feeling, and especially surface roughness fundamentally affect atopic customer decisions. Further, fabrics made from natural fibers (silk and linen) have a high potential to meet the needs of people with atopic dermatitis conditions. Both materials (M1, M7) show a combination of the high level of air permeability (more than 530 (mm . s−1)), a low level of water vapor resistance (in the range of 1.4–3.5 (m2 . Pa . W−1)) and provide very good subjective wearing comfort. Therefore, they can be substituted for traditional expert-recommended cotton.