BACKGROUND Stevens-Johnson syndrome (SJS) is a rare dermatologic disorder that is characterized by nonspecific flu-like prodrome with fever, malaise, myalgia, cough, rhinitis, and sore eyes, followed by a characteristic rash and mucocutaneous manifestations. It is triggered by medications in up to 80% of cases in adults. In each of these cases, the medication is oral or parenteral. Severe and progressive SJS can result in life-threatening complications. Adult-onset medication-induced SJS presents within 8 weeks of exposure to the offending substance, lasting 8 to 12 days. Recovery of denuded skin generally is complete within a month. There is no consensus on treatment, but supportive care with corticosteroids is often the initial intervention. CASE REPORT A 36-year-old woman with a flare of allergic rhinitis and tearing resistant to over-the-counter options was treated with topical ophthalmic ofloxacin. She began experiencing a diffuse mucocutaneous rash, with oral desquamation, tongue swelling, vaginal desquamation, and rash of the palms and soles within 24 h, which suggested the possibility of SJS. A skin biopsy was obtained, and pathology confirmed this suspicion. She was treated with parenteral antibiotics, corticosteroids, and supportive care, and after 10 days was discharged from the hospital. She had a complete recovery in 30 days. CONCLUSIONS The clinical course of SJS induced by the ophthalmic application of medication can be just as severe as the oral or parenteral routes. This is, to the best of our knowledge, the first documented case of SJS being triggered by topical ofloxacin.