A 33-year-old man with ankylosing spondylitis received secukinumab 150 mg monthly for 2 years. Approximately 1 year after initiation of treatment, recurrent sterile pustules appeared on the palms and soles, with minimal response to topical corticosteroids and calcipotriol. A week before seeking medical attention, new pustular lesions with itching, burning, and tenderness developed on the trunk and limbs. Histopathology showed subcorneal pustules in the epidermis and sparse lymphocytic infiltration in the dermis. A secukinumab-induced pustular reaction was diagnosed. After discontinuation of secukinumab and initiation of upadacitinib (15 mg/day), the pustules improved significantly in more than 1 month and the symptoms subsided. The case shows that IL-17A inhibitors can induce pustular skin reactions in patients with ankylosing spondylitis. Physicians should be alert for these adverse effects and adjust treatment.