Introduction β -lactams remain the most frequently reported cause of adverse drug reactions. Isolated adverse drug reactions to Clavulanate, a β -lactamase inhibitor added to Amoxicillin to form amoxicillin-clavulanate, remain rarer. Case Description A 62-year-old male heart transplant candidate due to complicated coronary artery disease presented with a previous anaphylactic reaction secondary to amoxicillin-clavulanate for a sinus infection. Skin testing to penicillin G, penicilloate, benzylpenicilloyl polylysine and amoxicillin was negative, followed by a negative oral provocation test to amoxicillin. At a subsequent visit, the patient had negative skin testing to non-irritant concentrations of amoxicillin-clavulanate (20 mg/ml) and ampicillin-sulbactam (20 mg/ml). Clavulanate without amoxicillin was not available for testing. However, upon oral challenge with full-dose amoxicillin-clavulanate, he developed urticaria on his upper back, left upper extremity (Figure 1) and chest and experienced bilateral hand flushing that resolved over the course of two hours with the administration of IM diphenhydramine, fexofenadine and montelukast. The patient was counseled to avoid all forms of β -lactamase inhibitors and use equally efficacious alternatives. Discussion While IgE-mediated hypersensitivity reactions to penicillin are more common, IgE-mediated hypersensitivity reactions to β-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam in isolation, have been reported. This case depicts an isolated β-lactamase inhibitor IgE-mediated reaction in the setting of previously negative skin testing. β -lactams remain the most frequently reported cause of adverse drug reactions. Isolated adverse drug reactions to Clavulanate, a β -lactamase inhibitor added to Amoxicillin to form amoxicillin-clavulanate, remain rarer. A 62-year-old male heart transplant candidate due to complicated coronary artery disease presented with a previous anaphylactic reaction secondary to amoxicillin-clavulanate for a sinus infection. Skin testing to penicillin G, penicilloate, benzylpenicilloyl polylysine and amoxicillin was negative, followed by a negative oral provocation test to amoxicillin. At a subsequent visit, the patient had negative skin testing to non-irritant concentrations of amoxicillin-clavulanate (20 mg/ml) and ampicillin-sulbactam (20 mg/ml). Clavulanate without amoxicillin was not available for testing. However, upon oral challenge with full-dose amoxicillin-clavulanate, he developed urticaria on his upper back, left upper extremity (Figure 1) and chest and experienced bilateral hand flushing that resolved over the course of two hours with the administration of IM diphenhydramine, fexofenadine and montelukast. The patient was counseled to avoid all forms of β -lactamase inhibitors and use equally efficacious alternatives. While IgE-mediated hypersensitivity reactions to penicillin are more common, IgE-mediated hypersensitivity reactions to β-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam in isolation, have been reported. This case depicts an isolated β-lactamase inhibitor IgE-mediated reaction in the setting of previously negative skin testing.