Abstract Background The hands are a common predilection site of atopic dermatitis (AD). Dupilumab is licensed for the treatment of AD but not for chronic hand eczema (CHE), while CHE is challenging to treat. Objectives To evaluate the long‐term effect of dupilumab on hand eczema (HE) in patients with AD from the BioDay Registry. Methods A prospective observational study of adult patients with HE, treated for AD with dupilumab. Patients with a HE severity of at least moderate at baseline were considered for analysis. Patients with other concomitantly systemic immunosuppressive treatments were excluded. Clinical effectiveness on HE severity, using the Hand Eczema Severity Index (HECSI) and photographic guide, and health‐related quality of life, using the Quality of Life in Hand Eczema Questionnaire (QOLHEQ), were evaluated. Results A total of 72 patients were included. HECSI‐75 was achieved by 54/62 patients (87.1%) and HECSI‐90 by 39/72 (62.9%) at 52 weeks. Based on the photographic guide, 56/62 patients (90.3%) achieved the endpoint of ‘clear’ or ‘almost clear’. Mean QOLHEQ reduction was −63.5% (95% confidence interval −38.23 to −27.41). There was no difference in response between HE subtypes. Conclusions The results from this study hold promise for dupilumab to be a suitable treatment option for isolated CHE.