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OBJECTIVE To determine the impact of a documented penicillin or cephalosporin allergy on the development of surgical site infections (SSIs). BACKGROUND Appropriate preoperative antibiotic prophylaxis reduces SSI risk, but documented antibiotic allergies influence the choice of prophylactic agents. Few studies have examined the relationship between a reported antibiotic allergy and risk of SSI and to what extent this relationship is modified by the antibiotic class given for prophylaxis. METHODS We conducted a retrospective cohort study of adult patients undergoing coronary artery bypass, craniotomy, spinal fusion, laminectomy, hip arthroplasty and knee arthroplasty at 3 hospitals from July 1, 2013, to December 31, 2017. We built a multivariable logistic regression model to calculate the adjusted odds ratio (aOR) of developing an SSI among patients with and without patient-reported penicillin or cephalosporin allergies. We also examined effect measure modification (EMM) to determine whether surgical prophylaxis affected the association between reported allergy and SSI. RESULTS We analyzed 39,972 procedures; 1,689 (4.2%) with a documented patient penicillin or cephalosporin allergy, and 374 (0.9%) resulted in an SSI. Patients with a reported penicillin or cephalosporin allergy were more likely to develop an SSI compared to patients who did not report an allergy to penicillin or cephalosporins (adjusted odds ratio, 3.26; 95% confidence interval, 2.71-3.93). Surgical prophylaxis did not have significant EMM on this association. CONCLUSIONS Patients who reported a penicillin or cephalosporin allergy had higher odds of developing an SSI than nonallergic patients. However, the increase in odds is not completely mediated by the type of surgical prophylaxis. Instead, a reported allergy may be a surrogate marker for a more complicated patient population.