BACKGROUND: Coronavirus disease-2019 (COVID-19) ranges from asymptomatic to severe. Several comorbidities are associated with worse clinical outcomes. Antibiotic use is common in COVID-19 and penicillin (PCN) allergy can affect antibiotic choice and may influence COVID-19 outcomes. OBJECTIVE: To investigate the impact of PCN allergy label on COVID-19 outcomes. METHODS: For this retrospective, cohort study, a Web-based tool for population cohort research, TriNetX, was used to identify adult COVID-19 patients with and without PCN allergy label. The two cohorts were matched using 1:1 propensity score matching for baseline demographics and conditions associated with risk for severe COVID-19. The 30-day risks for hospitalization, acute respiratory failure, intensive care unit requirement, mechanical ventilation requirement, and mortality were then compared between groups. Because bacterial infection can drive alternative antibiotic regimens, additional analyses focused on patients without bacterial infection. RESULTS: After propensity score matching, each cohort consisted of 13,183 patients. COVID-19 patients with PCN allergy had higher risks for hospitalization (risk ratio [RR] = 1.46; 95% confidence interval [CI], 1.41-1.52) acute respiratory failure (RR = 1.25; 95% CI, 1.19-1.31), intensive care unit requirement (RR = 1.20; 95% CI, 1.08-1.34), and mechanical ventilation (RR = 1.17; 95% CI 1.03-1.32) compared with patients without PCN allergy; however, there was no mortality difference (RR = 1.09; 95% CI, 0.96-1.23). Although the bacterial infection risk was higher in PCN allergic COVID-19 patients, exclusion of patients with bacterial infections yielded similar results. CONCLUSIONS: Penicillin allergic patients have higher risk for worse COVID-19 outcomes and should be considered for risk mitigation strategies.