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PURPOSE Case management (CM) is a promising intervention for frequent users of health care services. Our research question was how and under what circumstances does CM in primary care work to improve outcomes among frequent users with chronic conditions? METHODS We conducted a realist synthesis, searching MEDLINE, CINAHL, Embase, and PsycINFO (1996 to September 2017) for articles meeting the following criteria: (1) population: adult frequent users with chronic disease, (2) intervention: CM in a primary care setting with a postintervention evaluation, and (3) primary outcomes: integration of services, health care system use, cost, and patient outcome measures. Academic and gray literature were evaluated for relevance and robustness. Independent reviewers extracted data to identify context, mechanism, and outcome (CMO) configurations. Analysis of CMO configurations allowed for the modification of an initial program theory toward a refined program theory. RESULTS Of the 9,295 records retrieved, 21 peer-reviewed articles and an additional 89 documents were retained. We evaluated 19 CM interventions and identified 11 CMO configurations. The development of a trusting relationship fostering patient and clinician engagement in the CM intervention was recurrent in many CMO configurations. CONCLUSION Our refined program theory proposes that in the context of easy access to an experienced and trusted case manager who provides comprehensive care while maintaining positive interactions with patients, the development of this relationship fosters the engagement of both individuals and yields positive outcomes when the following mechanisms are triggered: patients and clinicians feel supported, respected, accepted, engaged, and committed; and patients feel less anxious, more secure, and empowered to self-manage., INTRODUCTION Frequent users of health care services are a small proportion of the population who account for a disproportionate number of visits to emergency departments, thereby placing a heavy strain [...]