Introduction: Tremendous advances in health care have been made through the development of evidence-based medicine (EBM). Studies show that physicians face barriers in practice, preventing the effective use of the best evidence available. Insight into these barriers should pave the way for an action plan to remove them. The aim of this study was to explore the major barriers to the practice of EBM by physicians in primary health care centers (PHCCs) and hospitals. Method: This cross-sectional study was conducted on physicians in PHCCs and Ministry of Health hospitals in the Dammam area (Dammam, Alkhobar, and Alqatief) of Saudi Arabia. A sample size of 409 physicians was chosen. Barriers to the practice of EBM and the reasons for not giving patients effective health care were investigated through questionnaires. Results: The response rate was 66.7%. The main barriers to practicing EBM stated by physicians were the lack of training in EBM (72.9%), facilities (34.4%), and time (29.2%). The least mentioned barriers were the lack of relevant evidence and the negative impact on medical skills (10.4% each). Discussion: Rather than skepticism about the concept, the main barriers to the use of EBM by physicians appeared to be a lack of knowledge and basic skills. Therefore, targeted education in EBM and a system that quickly delivers high-quality evidence are needed. This includes the allocation of an adequate infrastructure and time and the availability of relevant evidence.