© 2016 The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: firstname.lastname@example.org.Background The most common trigger for intraoperative anaphylaxis in Western Australia for the period 2014-5 was an antibiotic used for surgical prophylaxis, cefazolin. In these patients who subsequently present for surgery, alternative cephalosporins are forbidden by current guidelines because of concerns regarding an increased risk of anaphylaxis. However, consideration of the structure-activity relationships relevant to anaphylaxis suggests that cefalotin is a safe alternative because of structural dissimilarities, although there are no pubished clinical data relevant to the perioperative setting. Methods Patients diagnosed with intraoperative anaphylaxis to cefazolin at the Western Australian Anaesthetic Allergy Clinic were tested with intradermal cefalotin and, if negative, subsequently challenged i.v. If tolerated, cefalotin was recommended for subsequent surgery, and subjects were followed up to determine the safety of subsequent intraoperative doses. Results Twenty-one subjects diagnosed with immediate hypersensitivity to cephazolin, including 19 subjects with confirmed anaphylaxis, participated. None tested positive to intradermal cefalotin, and all received a graded i.v. challenge to cefalotin without developing signs or symptoms of anaphylaxis. Three subjects subsequently received intraoperative cefalotin 12-139 days later without adverse events. Conclusions A negative intradermal cefalotin skin test has a good negative predictive value in patients who have previously suffered anaphylaxis to cefazolin, allowing the rational and desirable use of this alternative cephalosporin for future surgery and the avoidance of less desirable antimicrobial agents.