BACKGROUND: Children with severe, persistent atopic eczema (AE) have limited treatment options, often requiring systemic immunosuppression. OBJECTIVE: To evaluate the effect of the temperature-controlled laminar airflow (TLA) treatment in children/adolescents with severe AE. METHODS: We recruited 15 children aged 2-16 years with longstanding, severe AE and sensitization to ≥1 perennial inhalant allergen. Run-in period of 6-10 weeks (3 visits), was followed by 12-month treatment with overnight TLA (Airsonett® , Sweden). The primary outcome was eczema severity (SCORAD-Index and Investigator Global Assessment-IGA). Secondary outcomes included child/family dermatology quality of life and family impact questionnaires (CDQLI, FDQLI, DFI), patient oriented eczema measure (POEM), medication requirements, and healthcare contacts. The study is registered as ISRCTN65865773. RESULTS: There was a significant reduction in AE severity ascertained by SCORAD and IGA during the 12-month intervention period (P<0.001). SCORAD was reduced from a median of 34.9 [interquartile range 28.75-45.15] at baseline to 17.2 [12.95-32.3] at the final visit, and IGA improved significantly from 4 [3-4] to 2 [1-3]. We observed a significant improvement in FDQLI (16.0 [12.25-19.0] to 12 [8-18], P=0.023) and DFI (P=0.011), but not CDQLI or POEM. Compared to 6-month period prior to enrollment, there was a significant reduction at six months after the start of the intervention in potent topical corticosteroids (P=0.033). The exploratory cluster analysis revealed two strongly divergent patterns of response, with 9 patients classified as responders, and 6 as non-responders. CONCLUSION AND CLINICAL RELEVANCE: Addition of TLA device to standard pharmacological treatment may be an effective add-on to the management of difficult-to-control AE. This article is protected by copyright. All rights reserved.