BACKGROUND: Drug allergy (DA) is one of the most important contributors to iatrogenic morbidity and mortality. Currently DA remains a major challenge for healthcare practitioners (HCPs). OBJECTIVE: To assess the knowledge, attitudes and practices of DA among HCPs in Central China. METHODS: A 25-item self-administered DA questionnaire were developed and applied in our study. The questionnaire covered 3 domains: knowledge, attitudes, and practice patterns. From July 2015 to October 2015, HCPs in 7 cities of Central China anonymously participated in the cross-sectional study. RESULTS: A total of 350 HCPs participated the study, 91 questionnaires uncompleted and 259 were analyzed. Among the respondents, 166 (64.1%) were doctors, 55 (21.2%) were nurses and 38 (14.7%) were medical students. The mean knowledge precision was 59.8%. HCPs agreed that drug induced immediate allergic reactions were IgE mediated (83.4%) and happened within 6 hours after drug administration (89.6%), and epinephrine was the first choice for drug induced anaphylaxis (79.5%). They also agreed that penicillin skin test was valuable to predict allergic reaction (88.4%). However, high proportion of HCPs (66.0%) believed glucocorticoids had an impact on drug skin test rather than antihistamines (4.2%), 47.1% never performed positive and negative control during skin test. More than 90% of the respondents would take patients' allergic history before drug administration, 98.8% agreed that they should receive advanced training of DA knowledge and practice. CONCLUSION: The HCPs demonstrated a low level of knowledge regarding DA. Advanced education is urgently needed for better understanding and filling the gaps exist in knowledge and clinical practice of DA.