The United States has invested substantially in technologies that enable health information exchange (HIE), which in turn can be deployed to reduce avoidable hospital readmission rates in many communities. With avoidable hospital readmissions as the primary focus, this study profiles successful hospital readmission rate reduction initiatives that integrate HIE as a strategy. We hypothesized that the use of HIE is associated with decreased hospital readmissions beyond other observed population health benefits. Results of this systematic review are used to describe and profile successful readmission reduction programs that integrate HIE as a tool.A systematic review of literature provided an understanding of the use of HIE as a strategy to reduce hospital readmission rates. We conducted a review of 4,862 citations written in English about readmission reduction strategies from January 2006 to September 2016 in the MEDLINE-PubMed database. Of these, 106 studies reported 30-day readmission rates as an outcome and only 13 articles reported using HIE.Only a very small number (12%) of hospitals incorporated HIE as a primary tool for evidence-based readmission reduction initiatives. Information exchange between providers has been suggested to play a key role in reducing avoidable readmission rates, yet there is not currently evidence supporting current HIE-enabled readmission initiatives. Most successful readmission reduction programs demonstrate collaboration with primary care providers to augment transitions of care to existing care management functions without additional staff while using effective information exchange capabilities.This research confirms there is very little integration of HIE into health systems readmissions initiatives. There is a great opportunity to achieve population health targets using the HIE infrastructure. Hospitals should consider partnering with primary care clinics to implement multifaceted transitions of care programs to significantly reduce 30-day readmission rates.