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Abstract Background Evidence-based medicine (EBM) is to integrate the best research evidence with our clinical expertise, circumstances, and unique values of our patient. However, there are no studies about using EBM in clinical practice among resident doctors in Syria. In this study, we aimed to evaluate the self-reported knowledge, attitude and practice (KAP) of EBM by resident doctors throughout different teaching hospitals in Syria. Methods The study is a cross-sectional. A self-reported online questionnaire was used to collect data about KAP of EBM from 214 resident physicians working in secondary and tertiary teaching hospitals. The study was conducted between September 2021 and February 2022. All data were analyzed using SPSS, and non-parametric statistical tests were used to identify the correlation between different variables and make the necessary comparisons. Results Two hundred and fourteen physicians responded to the questionnaire with a response rate of 85.6%. The overall mean scores of KAP of EBM were 59.2, 74.3 and 53.9%, respectively. The participants displayed a low level of awareness of resources and statistical terms used in EBM. The most well-known resources for residents were Up To Date and PubMed. Among the participants, pediatric residents achieved the highest score in practicing EBM, while family medicine residents scored the lowest score. Conclusion The overall impression about the KAP of EBM among Syrian residents was as following: weak awareness, neutral attitude and poor practice of EBM. Training workshops should be set up to teach residents the skills needed to move from opinion-based practice to evidence-based practice.