Objective: A growing body of evidence suggests that antibiotic allergy labels as documented in medical records are a risk factor for poor clinical outcomes. In this systematic review, we aimed to determine how antibiotic allergy labels influence 3 domains: antibiotic use and exposure, clinical outcomes, and healthcare-related costs. Design: We performed a systematic review to identify studies reporting outcomes in patients with antibiotic allergy labels compared to nonallergic counterparts. The search included PubMed, EMBASE, Cochrane CENTRAL, EBSCO, Cochrane Database of s of Reviews of Effects and Web of Science. Two reviewers independently screened studies for inclusion and abstracted data. Studies were graded using the Newcastle-Ottawa quality assessment scale. Study outcomes included antibiotic use, clinical outcomes, and economic outcomes. Results: In total, 41 studies met our criteria for inclusion. These studies varied in medical specialty, patient population, healthcare delivery system, and design, but most were conducted among adults age >18 years (85%) in the inpatient setting (82.5%). Among 34 studies examining antibiotic exposure, 32 (94%) found that patients with antibiotic allergy labels received more broad-spectrum antibiotics. Moreover, 31 studies examined clinical outcomes such as length of hospitalization, ICU admission, hospital readmission, multidrug-resistant or opportunistic infection, or mortality, and 27 (87%) found that allergy-labeled patients had at least 1 negative outcome. Of 9 studies examining healthcare costs, 7 (78%) found that allergy-labeled patients incurred significantly higher drug or hospital-related costs. Conclusions: Antibiotic allergy labels have negative effects on antibiotic use, clinical outcomes, and economic outcomes in a variety of clinical settings and populations.