Congress created the Patient Centered Outcomes Research Institute (PCORI) to fund comparative effectiveness research without encroaching on health care decision making in the private sector. This study asked if the organization's design is sufficient to insulate it from the hostile political environment that accompanied past comparative effectiveness research efforts. Data for the study came from key informant interviews, stakeholder interviews, content analysis of public comments, congressional hearings, and media and Internet content about PCORI. Drawing on theoretical frameworks of interest group behavior, the study assessed current and potential future stakeholder activity directed toward PCORI. The study found that PCORI's leadership has successfully mobilized patients and researchers in support of its mission. However, patient groups tend to mobilize within rather than across disease categories, limiting the collective impact these groups might have. Moreover, PCORI's success in including the patient voice in every stage of the research process has created only diffuse support for the organization. A lack of “practice-changing” findings—likely the result of the organization's interest group environment—leaves PCORI open to the criticism of ineffectiveness.