BACKGROUND: Surgical site infections are a major preventable source of morbidity, mortality, and increased healthcare expenditure following colorectal surgery. Patients with penicillin allergy may not receive the recommended preoperative antibiotics, putting them at increased risk for surgical site infections. OBJECTIVE: This study aimed to evaluate the impact of patient-reported penicillin allergy on preoperative antibiotic prophylaxis and surgical site infection rates among patients undergoing major colon and rectal procedures. DESIGN: Retrospective observational study. SETTING: Tertiary teaching hospital in Dallas. PATIENTS: Adults undergoing colectomy or proctectomy between July 2012 to July 2019. MAIN OUTCOME MEASURES: Preoperative antibiotic choice and surgical site infection. RESULTS: Among 2198 patients included in the study, 12.26% (n=307) reported a penicillin allergy. Patients with penicillin allergy were more likely to be white (82%) and female (54%) (p<0.01). The most common type of allergic reaction reported was rash (36.5%), whereas 7.2% of patients reported anaphylaxis. Patients with self-reported penicillin allergy were less likely to receive beta-lactam antibiotics compared to patients who did not report a penicillin allergy (79.8% vs 96.7%, p<0.001). Overall, there were 143 (6.5%) patients with surgical site infections. On multivariable logistic regression there was no difference in rates of surgical site infection between patients with penicillin allergy vs. those without penicillin allergy (adjusted odds ratio 1.14; 95% confidence interval, 0.71-1.82). LIMITATIONS: Retrospective study design. CONCLUSIONS: Self-reported penicillin allergy among colorectal surgery patients is common, however only a small number of these patients report any serious adverse reactions. Patients with self-reported penicillin allergy are less likely to receive beta-lactam antibiotics and more likely to receive non beta-lactam antibiotics. However, this does not affect the rate of surgical site infection among these patients and patient's penicillin allergy can be safely prescribed non beta-lactam antibiotics without negatively impacting surgical site infection rates. See Video Abstract at http://links.lww.com/DCR/B838 .