The diagnostic process of multiple nonsteroidal anti-inflammatory drug (NSAID)-induced hypersensitivity should result with providing the patient a safe alternative. However, concomitant reactivity to acetaminophen severely limits those options in children, as no approved drug is available especially for children below the age of 12. A 3-year-old boy developed facial angioedema with ibuprofen, ketoprofen, metamizole sodium, and acetaminophen, but tolerated tolmetin sodium, which is confirmed by a challenge test. He has also used it as an antipyretic during febrile infections without any reaction. This is the first report suggesting an approved drug, tolmetin sodium, as a safe alternative for multiple NSAID-concomitant acetaminophen-reactive children.