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Context. Case management interventions (CMIs) are recognized to improve patients' experience of integrated care, to promote better utilization of healthcare resources, and to reduce emergency department visits, hospitalizations and health care costs. However, contextual factors influencing implementation of CMIs in primary care settings in Canada still need to be studied. Objective. To examine facilitators and barriers influencing implementation planning, engagement of key actors and the start-up phases of a CMI led by nurse case managers for frequent users of healthcare services with chronic diseases and complex care needs. Study design. Qualitative multiple case study design. Setting. Six primary care clinics across four provinces in Canada. Population studied. Frequent users of healthcare services with chronic diseases and complex care needs. Intervention. A CMI led by nurse case managers that included four main components: 1) patient needs assessment; 2) care planning, including an individual services plan (ISP); 3) coordination of services among health and social services partners; 4) self-management support for patients and families. Methods. Data collection: in-depth interviews with nurse case managers (n=10), clinic managers (n=5), and other healthcare professionals (n=5); six focus groups with family physicians (n=20), and other healthcare professionals (n=8); and field notes by research coordinators. Analysis: Mixed descriptive thematic analysis; intra-case histories; systematic comparison among cases by means of a descriptive and interpretative matrix; investigator and patient partners triangulation. Outcome Measures. Factors influencing the implementation of the CMI in primary care settings. Results. Difficulty of access to patient hospital information is a common barrier to all cases, as well as identification and recruitment of patients with the greatest needs of a CMI. Nurse case managers need extra time in the short term, especially when preparing and conducting the ISP. On the other hand, a culture of patient-centredness and collaboration; managerial and clinical leadership and support; and a positive perception of the CMI alongside provider engagement helps to overcome these barriers. Conclusions. This study may help researchers, decision-makers and clinicians plan the implementation of CMIs in primary care settings for frequent users of healthcare services with chronic diseases and complex care needs., Competing Interests: Authors report none., (© 2021 Annals of Family Medicine, Inc.)