Background <p>Previous systematic reviews have examined the use of the 2009 version of the Consolidated Framework for Implementation Research (CFIR) in healthcare settings. However, these reviews primarily focused on studies conducted in secondary and tertiary care, with limited attention to its application in primary care.&#xa0;The use of the CFIR in primary care remains underexplored. Given the unique attributes of primary care—guiding principles such as first-contact care, continuity, comprehensiveness, coordination, and people-centeredness—findings from studies in other healthcare settings may not fully translate to the primary care context. This systematic review aimed to investigate how the CFIR has been applied in primary care, evaluate how it aligns with the guiding principles of primary care, and propose refinements to enhance its future application.</p> Methods <p>We searched Scopus and PubMed for publications including the terms CFIR and primary care from 2009 to February 15, 2024. We included studies that addressed clinical, organizational, or service delivery interventions implemented in primary care settings interventions within primary care settings. Data abstraction focused on several variables, including study design and location, participants, health topic, CFIR domains and constructs used, rationale for use, and additional implementation frameworks. We also evaluated how the applied constructs related to the WHO guiding principles of primary care.</p> Results <p>Out of 394 studies, 105 met the inclusion criteria. The use of the CFIR in primary care steadily increased between 2015 and 2024. Most studies were qualitative (80.9%), focused on non-communicable diseases (19%), conducted during the post-implementation phase (43.8%), centered on healthcare workers' perceptions (40%), and conducted in high-income country (83%). Most studies (61%) applied the five domains of the CFIR. However, 53.3% of the studies did not reported the rationale for selecting the domains. Some CFIR constructs investigated aligned with the guiding principles of primary care, particularly people-centeredness and comprehensiveness.</p> Conclusions <p>Refinements for applying the CFIR in primary care include enhancing community participation throughout the research process, from study design to interpretation and development of practice recommendations; reporting the rationale for selecting CFIR constructs, including their alignment with the guiding principles of primary care; increasing pre-implementation evaluation to support longitudinal, formative implementation research; and strengthening the role of implementation research in healthcare policies.</p> Systematic Review Registration <p>osf.io/4yq2f</p>