Background <p>Reported beta-lactam allergies often lead to avoidance of first-line antibiotics and may increase surgical complications. Cesarean sections (CSs), where prophylactic antibiotics are universally administered, offer a unique setting to assess the clinical impact of these labels on outcomes. The objective of this study was to investigate the impact of beta-lactam allergy labels on surgical site infection (SSI) rates and adherence to CS prophylactic antibiotic guidelines.</p> Methods <p>We performed a retrospective cohort study of all women undergoing CS at a secondary medical center between 2018 and 2023. Women with chorioamnionitis or missing antibiotic data were excluded. Patients were grouped by the presence or absence of a beta-lactam allergy label. For each group, we assessed 30-day SSI rates and adherence to prophylaxis guidelines (drug, dose, timing). Multivariable logistic regression identified independent predictors of SSI.</p> Results <p>Among 7,060 eligible women, 307 (4.3%) carried a beta-lactam allergy label. Not-per protocol antibiotic administered in 201/307 (65%) of labeled vs. 739/6,753 (11%) of unlabeled patients (<i>p</i> &lt; 0.001), mainly due to clindamycin monotherapy (88% of inadequate regimens). SSI rates were higher among labeled patients, 20/307 (6.5%) vs. 271/6,753 (4.0%) (<i>p</i> = 0.031). Among all patients, SSI occurred in 266/6,733 (3.9%) receiving cefazolin-based prophylaxis, 4/64 (6.3%) with clindamycin plus gentamicin, and 21/256 (8.2%) with inadequate regimens (<i>p</i> = 0.003). Beta-lactam allergy labeling independently increased SSI risk (aOR 1.68, 95% CI 1.05–2.71, <i>P</i> = 0.031).</p> Conclusions <p>Beta-lactam allergy labels were associated with an increased risk of SSI after cesarean section, due to suboptimal selection of prophylactic antibiotics. These findings underscore the importance of accurate allergy documentation and evidence-based perioperative antimicrobial stewardship to ensure optimal prophylaxis.</p>