Medical respite programs provide care to homeless patients who are too sick to be on the streets or in a traditional shelter, but not sick enough to warrant inpatient hospitalization. They are designed to improve the health of homeless patients while also decreasing costly hospital use. Although there is increasing interest in implementing respite programs, there has been no prior systematic review of their effectiveness. We conducted a comprehensive search for studies of medical respite program outcomes in multiple biomedical and sociological databases, and the grey literature. Thirteen articles met inclusion criteria. The articles were heterogeneous in methods, study quality, inclusion of a comparison group, and outcomes examined. Available evidence showed that medical respite programs reduced future hospital admissions, inpatient days, and hospital readmissions. They also resulted in improved housing outcomes. Results for emergency department use and costs were mixed but promising. Future research utilizing adequate comparison groups is needed.