Background: Drug allergy represents an important and growing public health problem worldwide. The clinical manifestations of drug allergy vary from mild to life threatening reactions. Objectives: To measure the level of knowledge and attitude of the resident physicians towards drug allergy and to determine factors that influence them. Method: A cross-sectional study was carried out among resident physicians at Zagazig University hospitals from February to April 2024. A self-administered questionnaire about knowledge and attitude towards drug allergy was completed by the study sample. Results: A total 248 residents were included in the current analysis; 146 medical specialties and 102 surgical specialties. The mean age was 29.1±1.8 years and 50.8% of the residents were females. Approximately 76% of the residents had insufficient knowledge and 49% had a negative attitude. In multivariate logistic regression of predictors of insufficient knowledge; shorter years of experience including <1 year, 1 to <2 years, 2 to <3 years (adjusted odds ratios [AOR] 10.31, 7.16, and 3.57, respectively), surgical specialties (AOR=3.38), lack of training in drug allergy (AOR=2.21), and not contributing to or observing any drug provocation test (AOR=5.72) were significantly independently associated with deficient knowledge. A statistically significant relation was found between attitude and dealing with patients who had drug allergy was found. Conclusions: Most of the resident physicians had insufficient knowledge about drug allergy while about half of them had a positive attitude. The research characterizes residents who are in need of specialized educational programs focusing on the mechanism, diagnosis, and management of drug allergies.