Background: Atopic dermatitis (AD) is aggravated by mechanical irritation and bacterial colonization. Objective: This study compared the efficacy of an antimicrobial silk fabric (DermaSilk®) with that of a topical corticosteroid in the treatment of AD. Methods: Fifteen children were enrolled and wore a dress, where the left side was made of DermaSilk and the right side was made of cotton. The right arm and leg were treated daily with the corticosteroid mometasone for 7 days. The treatment efficacy was measured with a modified EASI (Eczema Area and Severity Index) and with an assessment by the patients/parents and by a physician. All patients were evaluated at baseline, as well as 7 and 21 days after the initial examination. Results: All parameters showed that, irrespective of the treatment, there was a significant decrease of eczema after 7 days. No significant difference between DermaSilk-treated and corticosteroid-treated skin could be observed. Conclusion: DermaSilk showed potential to become an effective treatment of AD.