The management of recalcitrant atopic dermatitis (AD) is a challenging issue for both clinicians and patients. In this study, we evaluate the clinical efficacy and safety of double-filtration plasmapheresis (DFPP) in patients with recalcitrant AD. Eighteen patients with recalcitrant AD whose clinical condition had not been effectively controlled by current standard medical therapies were treated by either a single course of DFPP (N = 9) or with standard medical therapies only (N = 9). Clinical severity of AD was measured at baseline and at 1 and 4 weeks after treatment in patients in the DFPP group and at the corresponding time points in the control group using the standardized clinical severity scoring system for atopic dermatitis (SCORAD). In the nine patients who underwent DFPP, SCORAD values significantly decreased from 80.6 ± 16.7 (mean ± SD) at baseline to 65.9 ± 20.1 at 1 week and 69.8 ± 20.4 at 4 weeks after DFPP treatment (Wilcoxon signed-rank test, P < 0.05). No significant side-effects were observed during DFPP treatment. In the nine patients with recalcitrant AD who were treated with standard medical therapies, there were no significant differences between the SCORAD values at baseline (70.6 ± 13.9), 1 week (68.0 ± 14.4), and 4 weeks (69.8 ± 17.7) (P > 0.05). DFPP resulted in significant clinical improvements in patients with recalcitrant AD. Further studies are needed to evaluate the long-term clinical usefulness of DFPP in the treatment of patients with recalcitrant AD.