Having patients, doctors, health plan managers, hospital executives, and other stakeholders participate in the design of comparative effectiveness studies can ensure that this vital research focuses on the evidence gaps most relevant to health care decision makers. Through a qualitative assessment of case studies, we identify five key principles for the effective engagement of a broad coalition of participants in research intended to improve health care and control costs. Those principles are to ensure balance among the participating stakeholders; get participants to "buy in" to the process and understand their roles; provide neutral and expert facilitators for research discussions; establish connections among the participants; and keep the participants engaged throughout the research process.