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Intraoperative anaphylaxis is a life threatening and multiorgan system hypersensitivity reaction that frequently leads to cessation of operations. Despite the incidence of Cefazolin allergy being on the rise, the cases of anaphylaxis to Cefazolin during surgeries and its management are seldom reported.We present two patients with no known beta-lactam allergy and end stage kidney disease who received perioperative intravenous Cefazolin for planned deceased kidney transplant surgery at our academic medical center. Both patients developed anaphylaxes approximately three minutes following the administration of the antibiotic and experienced severe, refractory hypotension that required the use of vasopressors. The severity of the anaphylactic reactions resulted in the cessation of the transplant operation and multiple days of intensive care unit admission.Peri-or intraoperative anaphylaxis to Cefazolin is on the rise and its consequences in transplant candidates are even more dire given the pre-existing end organ failure, financial burden for health care system, potential loss of donor organs, and emotional burden for recipients and their families. These are the first two cases of reported Cefazolin-induced anaphylaxis that actually resulted in aborting the kidney transplant operation. In addition, cases of previously reported Type 1 hypersensitivity to Cefazolin as prophylaxis for operations were reviewed and the allergy workups were discussed.