Although co-trimoxazole is a major cause of fixed drug eruption, there are no reports in the literature of desensitization protocols for co-trimoxazole in such patients. We present the case of an 85-year-old woman with a fixed drug eruption to co-trimoxazole. Since she needed co-trimoxazole therapy for treatment of infection of a prosthetic hip by Staphylococcus aureus, she underwent allergy testing with co-trimoxazole and its components sulfamethoxazole and trimethoprim. Allergy tests were all negative and a diagnosis of nonallergic hypersensitivity reaction to co-trimoxazole was made. Based on previous experience, we decided to attempt a desensitization protocol with co-trimoxazole. After 10 days, the patient could receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice a day and no adverse reactions were observed. We suggest that desensitization protocols with co-trimoxazole be considered in patients with fixed drug eruption, especially when there are no alternative drugs.