The Clinical and Translational Science Award (CTSA) Workgroup for Comparative Effectiveness Research (CER) Education, Training, and Workforce Development identified a need to delineate the competencies that practitioners and users of CER for patient-centered outcomes research, should acquire. With input from CTSA representatives and collaborators, we began by describing the workforce. We recognize the workforce that conducts CER and the end users who use CER to improve the health of individuals and communities. We generated a preliminary set of competencies and solicited feedback from the CER representatives at each member site of the CTSA consortium. We distinguished applied competencies (i.e., skills needed by individuals who conduct CER) from foundational competencies that are needed by the entire CER workforce, including end users of CER. Key competency categories of relevance to both practitioners and users of CER were: (1) asking relevant research questions; (2) recognizing or designing ideal CER studies; (3) executing or using CER studies; (4) using appropriate statistical analyses for CER; and (5) communicating and disseminating CER study results to improve health. Although CER is particularly broad concept, we anticipate that these preliminary, relatively generic competencies will be used in tailoring curricula to individual learners from a variety of programmatic perspectives.