Infections at the incision site are a leading cause of postoperative complications, including death and higher medical costs, and they are also primarily avoidable. It is possible that patients with a penicillin allergy will not be given the appropriate preoperative antibiotics, increasing their chance of developing an infection at the surgical incision. Patient-reported penicillin allergy was investigated to determine its effect on antibiotic prophylaxis and surgical site infection rates in patients having major colon and rectal surgeries. The Dallas-based tertiary teaching hospital where this research took place. Between July 2012 and July 2019, adults with colectomy or proctectomy were considered. Antibiotic selection for prophylaxis and surgical site infection were the main indicators of success. There were a total of 2,198 patients in the trial, and 12.26% (n=307) of them reported being allergic to penicillin. The white race (82% of patients) and female gender (54% of patients; P<0.01) were significantly associated with penicillin allergy. Rash was reported by 36.5% of patients as the most frequent allergic response, whereas anaphylaxis was recorded by 7.2%. Beta-lactam antibiotics were prescribed to fewer patients who claimed a penicillin allergy (79.8% vs. 96.7%, P<0.001) compared to those who did not report a penicillin allergy. Surgical site infections affected 143 (6.5%) patients overall. There was no association between penicillin allergy and surgical site infection in multivariate logistic regression (adjusted OR 1.14; 95% CI, 0.71-1.82). The fact that the data was gathered in hindsight is a weakness of the research. Patients having colorectal surgery often report being allergic to penicillin; consequently, only a minority of these patients have any major adverse effects. Patients who report an allergy to penicillin are prescribed a different kind of antibiotic, 1 that does not include beta-lactamases. However, this does not reduce the incidence of surgical site infection among these patients, and non-beta-lactam antibiotics may be safely provided to these patients without lowering surgical site infection rates.