Background: More randomised control trials are required to assess the efficacy of traditional Chinese medicine. This multi-centre, randomised, assessor-blind, controlled study assessed the efficacy of the Chinese herbal formula Pei Tu Qing Xin Tang (PTQXT) for treating patients with atopic dermatitis (AD). Methods: Patients aged 5-25 years with moderate-to-severe AD were randomised to receive a 12-week treatment involving either oral administration of PTQXT; oral administration of PTQXT combined with an external application of Chinese herbs; or oral administration of antihistamine and a placebo of PTQXT pills added to topical I% mometasone furoate. The primary end-point measure was the change in the Scoring Atopic Dermatitis Index (SCORAD) at the end of the observation period, and secondary end-points included quality of life (QOL). The outcomes were evaluated at baseline, then every 4 weeks from week 4 to week 12 and every 8 weeks from week 12 to week 36. Results: Two hundred and seventy-five patients were recruited. During the 12-week treatment period, up to the primary end-point, the mean SCORAD decreased gradually in all three groups. At week 28 and week 36, there was a significantly greater decrease in the mean SCORAD for the Chinese herbal medicine-treated groups than for the control group (at week 28, P=0.002 and P=0.036, respectively; at week 36, P<0.001 and P=0.002, respectively). At week 36, the difference in QOL scores showed a significantly greater improvement in both Chinese herbal medicine-treated groups than in the control group (P<0.001 and P<0.001, respectively). Conclusions: PTQXT is effective in decreasing the severity of the disease and improving the QOL in patients with moderate-to-severe AD. Trial registration: Chinese Clinical Trial Registry: ChiCTR-TRC-08000156. 10 2015 Elsevier Ltd. All rights reserved.