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The Centers for Medicare and Medicaid Services (CMS) promulgated regulations commencing October 1, 2008, which deny payment for selected conditions occurring during the hospital stay and are not present on admission. Three of the 10 hospital-acquired conditions covered by the new CMS policy involve healthcare-associated infections, which are a common, expensive, and often preventable cause of inpatient morbidity and mortality.To outline a research agenda on the impact of CMS's payment policy on the healthcare system and the prevention of healthcare-associated infections.An invitational daylong conference was convened in April 2009. Including the planning committee and speakers there were 41 conference participants who were national experts and senior researchers.Building upon a behavioral model and organizational theory and management research a conceptual framework was applied to organize the wide range of issues that arose. A broad array of research topics was identified. Thirty-two research agenda items were organized in the areas of incentives, environmental factors, organizational factors, clinical outcomes, staff outcomes, and financial outcomes. Methodological challenges are also discussed.This policy is a first significant step to move output-based inpatient funding to outcome-based funding, and this agenda is applicable to all hospital-acquired conditions. Studies beginning soon will have the best hope of capturing data for the years preceding the policy change, a key element in nonexperimental research. The CMS payment policy offers an excellent opportunity to understand and influence the use of financial incentives for improving patient safety.