Dupilumab is a monoclonal antibody that targets interleukin (IL)-4 and IL-13 for use in moderate to severe eczema, asthma, and nasal polyposis. Our case report presents a 47-year-old woman with a history of nasal polyposis who developed angioedema after being treated with dupilumab for recurrent polyposis. She tolerated her first dose of dupilumab without reaction, but 10 days after her second injection, she developed swelling of the lips and forehead. She was treated with steroids with partial resolution. She received two further doses, which followed similar courses before dupilumab was discontinued. To the best of the authors' knowledge, this is the first report of dupilumab-associated angioedema in an adult. This report may be instructional for prescribers providing patients with anticipatory guidance or evaluating otherwise unexplained angioedema.