We present the unique case of a 33-year-old male referred to our clinic in search of analgesic options who was found to have a delayed hypersensitivity reaction to ibuprofen manifesting as a maculopapular rash and acute urticaria to acetaminophen. Non-steroidal anti-inflammatory drugs are associated with predictable reactions as well as immunoglobulin E-mediated reactions or T-cell mediated reactions. This case highlights the importance of knowledge of the different types of reactions to non-steroidal anti-inflammatory agents as well as the risk of cross reactivity. Delayed reaction to a single non-steroidal agent is rare; urticaria to acetaminophen is very rare. This is the first report we have found in the literature where one individual has a delayed reaction manifesting as rash to ibuprofen as well as urticaria to acetaminophen. We challenged our patient to aspirin which helped identify that his delayed reaction was only to ibuprofen and urticaria only to acetaminophen. The case also highlights the importance of an oral provocation challenge when no contraindications exist which helped us find that he could take celecoxib and avoid narcotics as initial therapy.