Objective Our objectives were to explore the changes in the level of interest in risk-sharing agreements (RSAs) in the EU during the last 15 years and the underlying reasons for these changes. Methods A systematic literature review was conducted using PubMed, Scopus, Web of Science, and Embase. Articles identified were divided into ‘quantitative articles’ used to establish the level of interest and ‘qualitative articles’ used to identify the underlying trends in RSAs. Results The literature search retrieved 2144 scientific articles. Data were extracted from 238 articles. Of these, 100 contained quantitative data and 138 contained qualitative data. The pace of articles being published about RSAs grew significantly in 2015, which related to the increase in interest in and knowledge about RSAs. The underlying reasons for the fluctuations were condensed into four overall themes: (1) push for value-based pricing, (2) economic crisis and further push to contain costs, (3) criticism of RSAs in the real world, and (4) diversification of RSAs to fit the purpose. Conclusion The overall level of interest in RSAs in the EU has been increasing since 2000; therefore, articles reporting the number of RSAs implemented and case studies have been steadily growing as evidence is becoming more readily available. The number of qualitative articles reporting and discussing the underlying reasons for these changes in interest has largely fluctuated over the last 15 years. Despite these fluctuations, interest in RSAs remains high.