Patients who did not receive preferred beta-lactam therapy due to reported beta-lactam allergy had an increased number of adverse events compared with patients without reported history of beta-lactam allergy.Methods.aEuro integral We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. Results.aEuro integral Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When beta-lactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28-7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62-2.87). Conclusions.aEuro integral Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.