Care coordination (CC) interventions involve systematic strategies to address fragmentation and enhance continuity of care. However, it remains unclear whether CC can sufficiently address patient needs and improve outcomes. We searched MEDLINE, CINAHL, Embase, Cochrane Database of Systematic Reviews, AHRQ Evidence-based Practice Center, and VA Evidence Synthesis Program, from inception to September 2019. Two individuals reviewed eligibility and rated quality using modified AMSTAR 2. Eligible systematic reviews (SR) examined diverse CC interventions for community-dwelling adults with ambulatory care sensitive conditions and/or at higher risk for acute care. From eligible SR and relevant included primary studies, we abstracted the following: study and intervention characteristics; target population(s); effects on hospitalizations, emergency department (ED) visits, and/or patient experience; setting characteristics; and tools and approaches used. We also conducted semi-structured interviews with individuals who implemented CC interventions. Of 2324 unique citations, 16 SR were eligible; 14 examined case management or transitional care interventions; and 2 evaluated intensive primary care models. Two SR highlighted selection for specific risk factors as important for effectiveness; one of these also indicated high intensity (e.g., more patient contacts) and/or multidisciplinary plans were key. Most SR found inconsistent effects on reducing hospitalizations or ED visits; few reported on patient experience. Effective interventions were implemented in multiple settings, including rural community hospitals, academic medical centers (in urban settings), and public hospitals serving largely poor, uninsured populations. Primary studies reported variable approaches to improve patient-provider communication, including health coaching and role-playing. SR, primary studies, and key informant interviews did not identify tools for measuring patient trust or care team integration. Sustainability of CC interventions varied and some were adapted over time. CC interventions have inconsistent effects on reducing hospitalizations and ED visits. Future work should address how they should be adapted to different healthcare settings and which tools or approaches are most helpful for implementation. PROSPERO #CRD42020156359.