Open research data sharing and reuse can bring more transparency to the research, save researcher time by preventing repetitive data collection processes, and lead to more collaborations. However, open research data sharing has not become common practice in some research fields such as Epidemiology due to a variety of issues. We propose that the negative impact of issues in front of open research data adoption can be tackled by the right institutional and infrastructural instruments. The objective of this study is to understand the roles that infrastructural and institutional instruments (or their combinations) can play in promoting open research data sharing and (re)use behavior in Epidemiology. To achieve this objective, first, we conducted a systematic review investigating what instruments could be used to lead researchers to open data practices. Then, to examine the availability and importance of the proposed instruments in Epidemiology, we conducted a case study that includes interviews with Epidemiology researchers and a research data management consultant who work at various University Medical Centers (UMCs) in the Netherlands. We also evaluated the transferability of our case study findings in a workshop with data stewards and research data officers that work in different research fields at a Dutch research university. To our best knowledge, this study is the first study that focuses on the field of Epidemiology while examining the roles of instruments in open research data adoption based on field-dependent characteristics. Our study shows that researchers in Epidemiology do not openly share or reuse research data due to many different reasons relating to the legal, cultural, technical, and organizational issues. Many of the potentially effective instruments are not fully within the reach of Epidemiology researchers. Researchers do not have sufficient access to research data managers, search engines with satisfactory functionality, overarching registries, and reward systems for data sharing contributions. Institutional instruments can support open research data adoption by reversing the lack of an open data sharing culture with the right incentivization approaches, by the provision of financing, and by actively supporting researchers via data stewards, research data managers, libraries, and data privacy officers. Infrastructural instruments have the potential for supporting open research data adoption by increasing the findability and interoperability of the research data, and making researchers’ interactions with data infrastructures easier. Our study shows that institutional instruments (especially those that target enhancing the open data sharing culture and creating data sharing incentives) are in a more vital position to open research data adoption. Nevertheless, considering that many instruments complement one another, to increase the effectiveness of the instruments, they should be combined. We recommend conducting case studies in other contexts (e.g. involving policymakers, infrastructure providers, etc.), considering that the issue that we examined in this research is a multi-actor issue and that in this single case study, we only focused on researchers.