Background: Inappropriate penicillin skin testing practices can worsen allergy mislabelling and antimicrobial resistance. This issue is likely more pronounced in Mainland China due to mandatory pre-emptive penicillin skin testing prior to any penicillin prescriptions. In contrast, Hong Kong follows guidelines more aligned with international recommendations on penicillin allergy testing. This study aimed to explore the disparities in drug allergy labelling, penicillin consumption, and antimicrobial resistance between Mainland China and Hong Kong. Methods: This multi-centre, real-world study analyzed drug allergy label prevalence, antibiotic use, and AMR between 2018 to 2022 in Mainland China and Hong Kong. Results: Penicillin allergy labels were significantly higher in Mainland China (47.13%) compared to Hong Kong (21.57%, p<0.01). Penicillin consumption was lower in Mainland China, where antimicrobial resistance to amoxicillin-clavulanate was also lower. Penicillin allergy delabeling rates were significantly higher in Mainland China (99.26%) compared to Hong Kong (93.13%, p=0.03). Conclusion: Significant differences in drug allergy labeling and antibiotic use between Mainland China and Hong Kong highlight the impact of non-evidence-based penicillin skin testing practices in Mainland China. Urgent reforms are needed to adopt international guidelines and reduce allergy mislabeling.