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Enfortumab vedotin is an antibody-drug conjugate against nectin-4 that is recently being used in the management of patients with urothelial carcinoma. The common adverse events include rashes, peripheral neuropathy, and hyperglycemia. Only a few cases of associated respiratory symptoms have been reported. Herein, we describe 2 patients with advanced urothelial carcinoma who experienced asthma exacerbation after initiating enfortumab vedotin treatment. Both patients improved with inhalation therapy. Since nectin-4 is expressed in the tracheal epithelium, its association with asthma is likely. This study highlights that clinicians should caution patients with a history of asthma against the worsening of respiratory symptoms when enfortumab vedotin is administered.