OBJECTIVE: To conduct a systematic review of studies of interventions that integrated medical and mental health care to improve general medical outcomes in individuals with serious mental illness. DATA SOURCES: English-language publications in MEDLINE (via PubMed), EMBASE, PsycINFO, and the Cochrane Library, from database inception through January 18, 2013, were searched using terms for our diagnoses of interest, a broad set of terms for care models, and a set of terms for randomized controlled trials (RCTs) or quasi-experimental design. Bibliographies of included articles were examined for additional sources. ClinicalTrials.gov was searched using the terms for our diagnoses of interest (serious mental illness,SMI,bipolar disorder,schizophrenia,orschizoaffective disorder) to assess for evidence of publication bias and ongoing studies. STUDY SELECTION: 4 RCTs were included from 1,729 articles reviewed. Inclusion criteria were RCT or quasi-experimental design; adult outpatient population with 25% or greater carrying a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder; intervention with a stated goal to improve medical outcomes through integration of care, using a comparator of usual care or other quality improvement strategy; and outcomes assessing process of care, clinical outcomes, or physical functioning. DATA EXTRACTION: A trained researcher abstracted the following data from the included articles: study design, funding source, setting, population characteristics, eligibility and exclusion criteria, number of subjects and providers, intervention(s), comparison(s), length of follow-up, and outcome(s). These abstracted data were then overread by a second reviewer. RESULTS: Of the 4 studies reviewed, 2 good-quality studies (according to the guidelines of the Agency for Healthcare Research and Quality) that evaluated processes of preventive and chronic disease care demonstrated positive effects of integrated care. Specifically, integrated care interventions were associated with increased rates of immunization and screening. All 4 RCTs evaluated changes in physical functioning, with mixed results: 2 studies demonstrated small improvements in the physical health component of the 36-Item Short-Form Health Survey (SF-36) and the 12-Item Short-Form Health Survey, and 2 studies demonstrated no significant difference in SF-36 scores. No studies reported on clinical outcomes related to preventive care or chronic medical care. CONCLUSIONS: Integrated care models have positive effects on processes of preventive and chronic disease care but have inconsistent effects on physical functioning for individuals with serious mental illness. The relatively small number of trials and limited range of treatment models tested and outcomes reported point to the need for additional study in this important area.