The Patient-Centered Outcomes Research Institute (PCORI) was established as part of the Affordable Care Act to promote research on the comparative effectiveness of treatment options. Advocates hoped this information would help reduce wasteful spending by identifying low-value treatments, but many conservatives and industry groups feared PCORI would ration care and threaten physicians' autonomy. PCORI faced three challenges during its first decade of operation: overcoming the controversy of its birth and escaping early termination, shaping medical practice, and building a public reputation for relevance. While PCORI has won reauthorization, it has not yet had a major impact on the decisions of clinicians or payers. PCORI's modest footprint reflects not only the challenges of getting a new organization off the ground but also the larger political, financial, and cultural barriers to the uptake of medical evidence in the US health care system. The growing attention among policymakers and researchers to provider prices (rather than utilization) as the driver of health care spending could be helpful to the political prospects of the evidence-based medicine project by making it appear to be less as rationing driven by costs and more as an effort to improve quality and uphold medical professionalism.