Eosinophilic otitis media (EOM) is an intractable otitis media mostly associated with bronchial asthma. Dupilumab, an anti-interleukin (IL)-4 receptor (R)α, is effective and has been approved for use in patients with moderate to severe bronchial asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyposis, whose diseases are not controlled by previous treatments including other molecular targeted drugs. We aimed to assess efficacy of dupilumab in three EOM patients with associated bronchial asthma, who were poor responders to previous topical and systemic corticosteroid therapy and molecular targeted therapies. Three patients with severe, refractory EOM (two with a granulation type) associated with bronchial asthma received dupilumab as add-on therapy for at least 6 months. The efficacy of dupilumab therapy was evaluated using severity scores, symptom scores, hearing acuities, temporal bone computed tomography (CT) scores, and surrogate markers before and after therapy. Severity scores in all patients were dramatically reduced to 2 points or less (full score: 16 points) after initiation of therapy. Air conduction hearing levels were improved in all patients. Temporal bone CT scores in two patients were reduced, and serum IgE levels in all three patients also decreased following therapy. We provide the first report that add-on dupilumab therapy was effective in patients with severe, refractory EOM who did not respond to the treatments including other molecular targeted therapy. Patients with severe middle ear mucosal change may benefit particularly from dupilumab therapy. Copyright © 2020. Published by Elsevier B.V.