Recently created in 2010, the Patient-Centered Outcomes Research Institute (PCORI) supports patient-centered comparative effectiveness research with a focus on prioritizing high-impact studies and improving trial design methodology. The Association of University Radiologists Radiology Research Alliance Task Force on patient-centered outcomes research in Radiology aims to review recently funded imaging-centric projects that adhere to the methodologies established by PCORI. We provide an overview of the successful application of PCORI standards to radiology topics, highlight how these methodologies differ from other forms of radiology research, and identify opportunities for new projects as well as potential barriers for involvement. Our hope is that review of specific case examples in radiology will clarify the use and value of PCORI methods mandated and supported nationally by the Affordable Care Act.