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Background: Vaccine effectiveness studies provide evidence on the effects of vaccines for preventing disease and the adverse outcomes following a vaccination rollout programme in a country or a specific population., Aims: To document the technical and capacity-building support provided by WHO to countries in the Eastern Mediterranean Region to conduct COVID-19 vaccine effectiveness studies., Methods: WHO implemented interventions to enhance the capacity of EMR countries to conduct COVID-19 vaccine effectiveness and similar epidemiological studies. The intervention consisted of several components, including methodological and technical support as well as data and project management at national and regional levels. Two WHO generic protocols were adopted: cohort study among healthcare workers and test-negative design in severe acute respiratory infections surveillance sites., Results: Egypt, Islamic Republic of Iran, Jordan, and Pakistan participated in the programme. The research protocols were adjusted to country context and settings. WHO provided technical, financial and infrastructure support, including the establishment of quality assessment approaches, study conduct, data management, report development, statistical data analysis, and experience-sharing between the countries. Technical capacity-building was also offered to other countries not involved in the vaccine effectiveness studies., Conclusion: COVID-19 pandemic provided an opportunity to enhance the research capacities of EMR countries for the conduct of vaccine effectiveness studies. The WHO consolidated efforts and its collaboration with countries resulted in enhancement of capacity and research infrastructure, especially in the 4 countries that were supported by this programme. The capacities acquired through the programme would be very useful for other vaccine-preventable communicable diseases, thus better informing national immunization programmes and policies in EMR countries., (Copyright © Authors 2023; Licensee: World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)