For more than 20 years, the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program has been identifying and synthesizing evidence to inform evidence-based healthcare. Recognizing that many healthcare settings continue to face challenges in disseminating and implementing evidence into practice, AHRQ's EPC program has also embarked on initiatives to facilitate the translation of evidence into practice and to measure and monitor how practice changes impact health outcomes. The program has structured its efforts around the three phases of the Learning Healthcare System cycle: knowledge, practice, and data. Here, we use a topic relevant to the field of hospital medicine-Clostridium difficile colitis prevention and treatment-as an exemplar of how the EPC program has used this framework to move evidence into practice and develop systems to facilitate continuous learning in healthcare systems.