RATIONALE Over the last decade, in order to close the safety and health care quality chasm, there has been a growing imperative to translate evidence-based research into practice. AIMS AND OBJECTIVES This study examines the major facilitators and barriers of implementing in a large US insurance organization – Aetna Corporation – an evidence-based model of care, the Transitional Care Model, which has been rigorously tested over the past twenty years by a multidisciplinary team at the University of Pennsylvania. METHODS Semi-structured interviews of 19 project leaders, case managers, and transitional care nurses were conducted during two phases of translation – start-up and roll out. Qualitative analysis was used to identify more than a dozen key barriers to and facilitators of translation in these two critical phases. Results Six facilitators and seven barriers that are consistent with the literature were identified during and categorized as either start-up or roll-out. CONCLUSION The combined results have important practical implications for other, subsequent translational efforts and for assisting providers, policy makers, payers, and other change agents in integrating evidence-based practice with “real world” management.