Background: Currently there is no cure for severe atopic dermatitis (AD). Wet-wrap therapy (WWT) has also been used to treat pediatric AD and shown a satisfactory effectiveness, but clinical evidence supporting the use of WWT on severe adult AD is still insufficient. Methods: Twelve patients (eight men and four women) with severe AD (SCORing Atopic Dermatitis [SCORAD] score >= 50) treated between January 2015 and September 2017 in our hospital were included. The patients underwent WWT (daily dose: 15g halometasone cream+100g Vaseline ointment) twice daily for 2h/session for 7 days. SCORAD, visual analog scale (VAS) for pruritus, investigator's global assessment (IGA), dermatology life quality index (DLQI) scores and serum cortisol levels were determined before and after the WWT. Results: The patients (mean age: 58.9 +/- 18.9 years; range: 27-85 years) had a median disease duration of 27.5 months. After the WWT, the average scores of SCORAD (28.79 +/- 5.16 vs. 68.59 +/- 8.61, 95%CI: 35.18-44.42), VAS (2.75 +/- 0.62 vs. 7.5 +/- 1.17, 95%CI: 4.14-5.36), IGA (1.83 +/- 0.39 vs. 4.08 +/- 0.51, 95%CI: 1.96-2.54), and DQLI score (8.33 +/- 1.83 vs. 13.83 +/- 2.79, 95%CI: 4.16-6.84) reduced significantly compared with the scores before the WWT (All P<0.001). However, serum cortisol levels were not affected significantly by the WWT. Four patients complained of tolerable wet dressing-associated discomforts, which was resolved after the wet dressing was removed when the WWT was completed. For the 85-year-old man, serum cortisol levels were lower than the normal value after the WWT (3.67 mu g/dL) but restored to the normal levels (13.44 mu g/dL) 2 weeks after the WWT was ended. No other adverse events occurred. Conclusion: WWT can relieve pruritus, reduce skin lesions, and improve quality of life in adult patients with severe AD. Thus, WWT may be effective and safe for severe adult AD.