Background: Despite growing interest in patient engagement in research, there are few empirical investigations of the nature of engagement and its effects. This information is important, not only to inform practical decisions researchers and funders must make, but also to inform discussion of the ethical implications of engaging patients, which has received little attention to date. Methods: The aim of this study was to characterize patient engagement in research funded by the Patient-Centered Outcomes Research Institute (PCORI) as a step toward enhancing current understanding of the nature and effects of engagement and prompting an in-depth consideration of the ethical implications of engaging patients in research. Qualitative interviews were conducted with 19 PCORI-funded principal investigators and with 33 patients engaged in 18 of the same 19 projects. Results: Reasons cited for engaging patients included to enhance relevance and feasibility and to improve dissemination. While engagement occurred at different points during the research, patients were most commonly engaged in reviewing study materials and less commonly engaged at earlier points. Engagement varied by approach, frequency of interaction, and the extent to which patient input changed the research. Impacts of engagement included improving the relevance, feasibility, acceptability, and quality of the research. Conclusion: Our findings on the nature and impacts of engagement have importance not only for practical questions researchers, funders, and patients might raise, but also for several ethical considerations regarding patient engagement related to why patients are engaged, the kinds of patients engaged, when patients are engaged, and how patients are engaged. We discuss our findings in consideration of the main ethical issues they imply, including ethical rationales for engagement, justice-related concerns, and ethical concerns arising from when and how patients are engaged. As efforts to engage patients increase, this discussion provides insights that researchers, funders, and patients may find valuable.