BACKGROUND: Patients who have failed traditional treatment of chronic urticaria may require trials of alternative medications. Safety profiles, continuous laboratory monitoring, and physician comfort are often barriers to treatment. OBJECTIVES: To evaluate the safety of alternative agents used in chronic urticaria. METHODS: A retrospective chart review of electronic medical records from a single-center allergy and immunology clinic in a major academic hospital was conducted. One hundred twenty-six charts of patients with chronic urticaria treated with alternative agents were reviewed. RESULTS: Adverse effects were reported in 39 of 73 (53%) patients on dapsone, 19 of 47 (40%) patients on sulfasalazine, 15 of 36 (42%) patients on tacrolimus, 7 of 45 (16%) patients on hydroxychloroquine, 9 of 27 (33%) patients on mycophenolate, 6 of 8 (75%) patients on cyclosporine, and 3 of 24 (4%) patients on omalizumab. Most of these adverse effects were mild, did not require discontinuation of the medication, and resolved after stopping the medication or decreasing the dose. CONCLUSIONS: The use of alternative agents for the treatment of chronic urticaria angioedema is generally safe when proper laboratory and clinical monitoring is observed. (C) 2016 American Academy of Allergy, Asthma & Immunology