Introduction: The Danish Anaesthesia Allergy Centre (DAAC) investigated 89 adult patients with suspected perioperative cefuroxime-associated hypersensitivity reactions between 2004 and 2013. The goals were to determine whether the time to index reaction after cefuroxime exposure could be used to implicate cefuroxime as the cause of the reactions and explore different test modalities in diagnosing cefuroxime hypersensitivity. Method: Skin tests, in vitro tests, and titrated provocations were used to determine cefuroxime hypersensitivity. Patients were deemed cefuroxime positive on the basis of at least two positive tests and/or a positive provocation. Results: One or more tests were positive for cefuroxime in 24 of 89 (27.0%) patients. One was only specific IgE positive and was deemed cefuroxime negative. Twenty-three (25.8%) were deemed cefuroxime positive. There were four specific IgE-, 4 histamine release test-, 13 skin test-, and 14 provocation positive patients. There were eight (34.8%) patients who were only provocation positive. Data on time to index reaction after cefuroxime exposure were available for 80 patients (22 in the positive group and 58 in the negative group), 22 of 22 (100%) of positive patients reacted in <15 min vs. only 38 of 58 (65.5%) of negative patients. Conclusion: All patients with confirmed hypersensitivity to cefuroxime reacted within 15 min of administration, but so did 65.5% of Cefuroxime negative patients, making timing of administration an unreliable predictor of causation in the perioperative setting. Provocations were always positive when carried out in skin test positive patients; however, eight patients had positive provocations only, highlighting the need for provocation in skin test negative patients.