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Suspected penicillin allergic individuals receive suboptimal non-β-lactams for intraoperative prophylaxis which may prolong operations and have negative clinical outcomes. We therefore studied if β-lactam de-labeling optimized choice of prophylactic antibiotics and improved intraoperative time efficiency.A multistep approach was used. It included a risk assessment tool by an allergist, β-lactam skin testing and oral provocation. To determine the value of de-labeling, we appraised intraoperative antibiotic choices and correlated them with time to first incision.A total of 194 patients were evaluated preoperatively. Four patients were diagnosed β-lactam allergic on skin testing. Of the remaining 190 skin test negative patients, 146 were β-lactam challenged. Only 5% reacted and were considered β-lactam allergic. Cefazolin became the perioperative antibiotic of choice for 77% of patients requiring antibiotic prophylaxis. Only 5 confirmed β-lactam allergic patients received intraoperative vancomycin. Patients avoiding use of vancomycin saved an average of 22 minutes in operative time. Of the 44 patients not having a β-lactam challenge, 36 received antibiotics and 18 (50%) of these were prescribed intraoperative cefazolin.Using this three step process, almost all of those claiming penicillin allergy were de-labeled. In most patients that were drug challenged, β-lactam antibiotics became the perioperative drug of choice. In cases where oral challenge was not used in the assessment only 50% were given a β-lactam. The reduced use of vancomycin minimized delays in initiation of incision time, thus improving operative efficiency. Ultimately, randomized controlled studies are required to objectively determine the effectiveness of this approach.