Background: Familial hypercholesterolemia (FH) affects more than one million Americans, and most individuals have not been formally diagnosed with the condition. Individuals with FH have markedly elevated serum low-density lipoprotein cholesterol (LDL-C) levels from birth that substantially increase their risk for early-onset cardiovascular (CV) events. Guideline-recommended treatments exist to lower LDL-C and reduce the risk of CV events in individuals with FH and hypercholesterolemia. This study seeks to address a significant gap in the care of individuals with FH by systematically developing an effective approach to increase the adoption of guideline-recommended treatments for FH. Methods: This developmental study will consist of three aims: 1) determine the barriers to and facilitators of treatment of FH; 2) develop a list of potential implementation strategies to promote the adoption of guideline-recommended treatment of individuals with FH, and 3) pilot one implementation strategy from Aim 2 in one health care system to evaluate implementation outcomes of the strategy. The Practical, Robust Implementation and Sustainability Model will guide this project, including the development of interview questions, implementation strategies, and evaluation of the implementation strategy. The implementation outcomes include: of individuals targeted by the implementation strategy, how many are impacted by it (reach), measure the change in knowledge, attitude, and behavior that is impacted by the implementation strategy (effectiveness), in settings targeted by the implementation strategy, how many adopt it (adoption), and fidelity and cost of the implementation strategy (implementation). Data sources will include electronic health records, administrative databases, surveys, and semi-structured interviews. Discussion: The inclusion of patient and organizational stakeholder experiences is a critically important step in developing efficient and effective implementation strategies. Additionally, perspectives from a variety of geographic areas and cultural perspectives should increase feasibility and fidelity of the interventional approach to improve adoption of guideline-recommended practices for FH care.