Abstract Background In Belgium, the construction of the national electronic point-of-care information service, EBMPracticeNet, was initiated in 2011 to optimize quality of care by promoting evidence-based decision-making. The collaboration of the government, healthcare providers, Evidence-Based Medicine (EBM) partners, and vendors of Electronic Health Records (EHR) is unique to this project. All Belgian healthcare professionals get free access to an up-to-date database of validated Belgian and nearly 1,000 international guidelines, incorporated in a portal that also provides EBM information from sources other than guidelines, including computerized clinical decision support that is integrated in the EHRs. The EBMeDS system is the electronic evidence-based decision support system of EBMPracticeNet. The EBMeDS system covers all clinical areas of diseases and could play a crucial role in response to the emerging challenge posed by chronic conditions. Diabetes was chosen as the analysis topic of interest. The objective of this study is to assess the effectiveness of EBMeDS use in improving diabetes care. This objective will be enhanced by a formal process evaluation to provide crucial information on the feasibility of using the system in daily Belgian family medicine. Methods The study is a cluster-randomized trial with before/after measurements conducted in Belgian family medicine. Physicians’ practices will be randomly assigned to the intervention or control group in a 1:1 ratio, to receive either the EBMeDS reminders or to follow the usual care process. Randomization will be performed by a statistical consultant with an electronic random list generator, anonymously for the researchers. The follow-up period of the study will be 12 months with interim analysis points at 3, 6 and 9 months. Primary outcome is the one-year pre- to post-implementation change in HbA1c. Patients will not be informed about the intervention. Data analysts will be kept blinded to the allocation. Discussion The knowledge obtained in this study will be useful for further integration in other Belgian software packages. Users’ perceptions and process evaluation will provide information for improving the feasibility of the system. Trial registration The trial is registered with the ClinicalTrials.gov registry: NCT01830569 .