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Introduction: Continuing medical education (CME) is meant to drive and support improvements in practice. To achieve this goal, CME activities must move beyond simply purveying knowledge, instead helping attendees to contextualize information and to develop strategies for implementing new learning. CME attendees face different barriers to implementing learning, depending on both personal and practice specific contexts. We sought to develop a framework, applicable across multiple CME activities, for categorizing barriers that learners anticipated encountering after CME activities. Methods: Building on previous work, qualitative research methods were used to develop an enhanced framework classifying attendee-perceived barriers to implementing CME learnings in practice. Three thousand one hundred thirty (3130) narrative responses on attendee-perceived barriers to implementing learnings were collected from 75 Kaiser Permanente Colorado live CME activities for family medicine, internal medicine, pediatric, and OB/GYN clinicians in 2008 and 2009. Results: Our CME Learning Transfer Barrier Framework contains 27 discrete barriers in 12 barrier categories (including "none"). The barrier framework was applicable across two years of live CME activities for different clinician target audiences. Discussion: Assessing, characterizing, and summarizing barriers to implementing learning during CME activities can provide valuable information to inform subsequent CME interventions, and provide feedback to organizational leaders to inform performance improvement efforts. The framework may be applicable to other CME formats and to CME activities for audiences in different practice settings. (Contains 2 tables and 3 figures.)