BACKGROUND Multicomponent, interdisciplinary intensive primary care programs target complex patients with the goal of preventing hospitalizations, but programs vary, and their effectiveness is not clear. In this study, we systematically reviewed the impact of intensive primary care programs on all-cause mortality, hospitalization, and emergency department use. METHODS We searched PubMed, CINAHL, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Reviews of Effects from inception to March 2017. Additional studies were identified from reference lists, hand searching, and consultation with content experts. We included systematic reviews, randomized controlled trials (RCTs), and observational studies of multicomponent, interdisciplinary intensive primary care programs targeting complex patients at high risk of hospitalization or death, with a comparison to usual primary care. Two investigators identified studies and abstracted data using a predefined protocol. Study quality was assessed using the Cochrane risk of bias tool. RESULTS A total of 18 studies (379,745 participants) were included. Three major intensive primary care program types were identified: primary care replacement (home-based; three RCTs, one observational study, N = 367,681), primary care replacement (clinic-based; three RCTs, two observational studies, N = 9561), and primary care augmentation, in which an interdisciplinary team was added to existing primary care (five RCTs, three observational studies, N = 2503). Most studies showed no impact of intensive primary care on mortality or emergency department use, and the effectiveness in reducing hospitalizations varied. There were no adverse effects reported. CONCLUSIONS Intensive primary care interventions demonstrated varying effectiveness in reducing hospitalizations, and there was limited evidence that these interventions were associated with changes in mortality. While interventions could be grouped into categories, there was still substantial overlap between intervention approaches. Further work is needed to identify program features that may be associated with improved outcomes.