Background Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking.Objectives To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment.Methods A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed-effects models to determine changes over time.Results We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23 center dot 8 vs. 14 center dot 8), while baseline Patient-Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan.Conclusions Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients.