ABSTRACT: Importance:Allergy to ?-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic- and region-specific sensitization patterns of skin testing for ?-lactam antibiotic allergy are also unknown. Objective:To identify the prevalence, 1-year incidence, and sensitization patterns of ?-lactam antibiotic allergy in patients in Hong Kong. Design, Setting, and Participants:This cross-sectional study obtained territorywide, anonymized electronic patient data from the Clinical Management Systems of the Hospital Authority, the sole publicly funded health care system in Hong Kong with facilities in 7 regions (Hong Kong East, Hong Kong West, Kowloon Central, Kowloon East, Kowloon West, New Territories East, and New Territories West). All referrals to Queen Mary Hospital for ?-lactam antibiotic allergy testing from January 1, 2018, to December 31, 2019, were also analyzed for sensitization patterns. Main Outcomes and Measures:Prevalence and cumulative incidence of ?-lactam antibiotic allergy reported in Hong Kong, and sensitization patterns according to ?-lactam antibiotic allergy skin testing. Results:Complete records of 7?184?271 unique patients were analyzed, with a men to women ratio of 1:1.2 and with a median age of 44 years. The prevalence of physician-reported ?-lactam antibiotic allergy was 2.0%, and the cumulative incidence was 107 per 100?000 population. Of the 34?402 new drug allergies reported in 2018, 8032 (23.3%) were ?-lactam antibiotic allergies. Three hundred fifty-five patients with reactions suggestive of ?-lactam antibiotic allergy underwent skin testing, and only 49 (13.8%; 95% CI, 10.64%-17.90%) of them had positive test results. Of these 49 patients, 14 (28.6%; 95% CI, 18.35%-44.49%) had selective reaction and 35 (71.4%; 95% CI, 59.84%-85.27%) had nonselective reaction. The sensitization rate to either benzylpenicilloyl polylysine or a minor determinant (benzylpenicilloate) was 47.0% (n?=?23; 95% CI, 34.85%-63.21%), with 10 patients monosensitized to benzylpenicilloyl polylysine only (20.4%; 95% CI, 11.74%-35.48%) and 5 to benzylpenicilloate only (10.2%; 95% CI, 4.45%-23.42%). Conclusions and Relevance:Results of this study suggest that patients in Hong Kong with ?-lactam antibiotic allergy had much higher rates of monosensitization to benzylpenicilloyl polylysine and benzylpenicilloate, making these reagents essential in ?-lactam antibiotic skin tests. Such a finding warrants future studies into whether this sensitization is specific to ethnicity or region.