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Background: Evidence-based medicine (EBM) bridges research and clinical practice to enhance medical knowledge and improve patient care. However, clinical decisions in many African countries don't base on the best available scientific evidence. Hence, this study aimed to determine the effect of training interventions on background knowledge and awareness of EBM sources, attitude, competence, and practice of EBM among healthcare professionals. Method: We designed a controlled group quasi-experimental pre-post test study to evaluate the effect of capacity-building EBM training. A total of 192 healthcare professionals were recruited in the study (96 from the intervention and 96 from the control group). We used a difference-in-differences (DID) analysis to determine the effect of the training. Along the way, we used a fixed effect panel-data regression model to assess variables that could affect healthcare professionals' practice of EBM. The cut point to determine the significant effect of EBM training on healthcare professionals' background knowledge and awareness of EBM sources, attitude, and competence was at a P-value < 0.05. Result: The DID estimator showed a significant net change of 8.0%, 17.1%, and 11.4% at P < 0.01 on attitude, competence, and practice of EBM, respectively, whereas no significant increment in the background knowledge and awareness of EBM sources. The fixed effect regression model showed that the attitude [OR = 2.288, 95% CI: (1.049, 4.989)], competence [OR = 4.174, 95% CI: 1.984, 8.780)], technical support [OR = 2.222, 95% CI: (1.043, 3.401)], and internet access [OR = 1.984, 95% CI: (1.073, 4.048)] were significantly affected EBM practice. Conclusion: The capacity-building training improved attitude, competence, and EBM practice. Policymakers, government, and other concerned bodies recommended focusing on a well-designed training strategy to enhance the attitude, competence, and practice towards EBM among healthcare professionals. It was also recommended to enhance internet access and set mechanisms to provide technical support at health facilities. [ABSTRACT FROM AUTHOR]