Surgical site infection (SSI) is a common postprocedure complication that may be prevented by adhering to established recommendations, including administration of preoperative antibiotic prophylaxis. Patients with a β-lactam allergy (BLA) label have an increased risk of SSI. We sought to evaluate the appropriateness of preoperative antibiotic prophylaxis in patients labeled with a BLA compared those without a BLA. This was a single-center, retrospective, matched cohort study of adult patients who underwent a clean or clean-contaminated knee replacement, abdominal hysterectomy, colorectal surgery, or coronary artery bypass graft (CABG). Patients with a BLA label were matched to patients without a BLA label based on procedure, age, and body mass index (BMI). The primary end point was the rate of appropriate preoperative antibiotic prophylaxis, including antibiotic selection and timing prior to incision. In total, 260 patients were included. Knee replacement (38%) was the most common procedure, followed by abdominal hysterectomy (25%), colorectal surgery (18%), and CABG (18%). Appropriate preoperative antibiotic prophylaxis was higher among patients without a BLA (76% vs 37%; P < .001). Among patients with a mild-to-moderate reaction or intolerance, 29 (53%) received antibiotics that would have been appropriate only if the patient had had a severe BLA. Patients with a BLA were more likely to have had an antibiotic omitted from the prophylactic regimen (44% vs 4%; P < .001). Patients with a BLA were more likely to receive inappropriate preoperative antibiotic prophylaxis, attributed to misinterpretation of BLA labels and antibiotic omissions. Optimizing antibiotic prophylaxis among patients with BLAs remains an area of opportunity to prevent SSIs.