Background: Drug hypersensitivity (DH) is potentially life threatening. Its management in the emergency department (ED) is not always satisfactory. Previous studies have evaluated the management of allergic reactions in the ED, but none has specifically addressed patients with known DH. In this study we aimed to analyze the treatment offered to patients with DH presenting to the ED in a hospital in Israel for any reason. Methods: Records of patients discharged from the ED on 19 randomly chosen dates between February 2004 and September 2005 were retrospectively reviewed. Data included demographics, diagnosis, previous drug allergies, training of the ED physician, time and day of the week, management, and discharge instructions. Results: Of 3,996 admissions to the ED, 436 (11%) patients reported 531 hypersensitivities, 45 (10%) of which were treated incorrectly. Trainees in internal medicine made significantly fewer errors than did trainees in surgery (p < 0.0005). Most errors involved NSAID hypersensitivity. Conclusion: A known DH was overlooked in 45 patients admitted to the ED. The specialty of the treating physician was the only significant factor found to affect patient management. Physicians, especially surgeons, should receive guidance concerning the correct management of patients with DH. All physicians should be aware of the optimal management of these patients.