Background: De-implementation or abandonment of ineffective or low-value healthcare is becoming a priority research field globally due to the growing empirical evidence of the high prevalence of such care and its impact in terms of patient safety and social inefficiency. Little is known, however, about the factors, barriers, and facilitators involved or about interventions that are effective in promoting and accelerating the de-implementation of lowvalue healthcare. The De-imFAR study seeks to carry out a structured, evidence-based, and theory-informed process involving the main stakeholders (clinicians, managers, patients, and researchers) for the design, deployment, and assessment of de-implementation strategies for reducing low-value pharmacological prescribing. Methods: A phase I formative study using a systematic and comprehensive framework based on theory and evidence for the design of implementation strategies-specifically, the Behavior Change Wheel (BCW)-will be conducted to design and model de-implementation strategies to favor reductions in low-value pharmacological prescribing of statins in primary prevention of cardiovascular disease (CVD) by main stakeholders (clinicians, managers, patients, and researchers) in a collegiate way. Subsequently, a phase II comparative hybrid trial will be conducted to assess the feasibility and potential effectiveness of at least one active de-implementation strategy to reduce low-value pharmacological prescribing of statins in primary prevention of CVD compared to the usual procedures for dissemination of clinical practice guidelines ("what-not-to-do" recommendations). A mixed-methods evaluation will be used: quantitative for the results of the implementation at the professional level (e.g., adoption, reach and implementation or execution of the recommended clinical practice); and qualitative to determine the feasibility and perceived impact of the de-implementation strategies from the clinicians' perspective, and patients' experiences related to the clinical care received.