IMPORTANCE Determining innovative approaches that better align health needs to the appropriate setting of care remains a key priority for the transformation of US health care; however, to our knowledge, no comprehensive assessment exists of alternative management strategies to hospital admission for acute medical conditions. OBJECTIVE To examine the effectiveness, safety, and cost of managing acute medical conditions in settings outside of a hospital inpatient unit.EVIDENCE REVIEW MEDLINE, Scopus, CINAHL, and the Cochrane Database of Systematic Reviews (January 1995 to February 2016) were searched for English-language systematic reviews that evaluated alternative management strategies to hospital admission. Two investigators extracted data independently on trial design, eligibility criteria, clinical outcomes, patient experience, and health care costs. The quality of each review was assessed using the revised AMSTAR tool (R-AMSTAR) and the strength of evidence from primary studies was graded according to the Oxford Centre for Evidence-Based Medicine.FINDINGS Twenty-five systematic reviews (representing 123 primary studies) met inclusion criteria. For outpatient management strategies, several acute medical conditions had no significant difference in mortality, disease-specific outcomes, or patient satisfaction compared with inpatient admission. For quick diagnostic units, the evidence was more limited but did demonstrate low mortality rates and high patient satisfaction. For hospital-at-home, a variety of acute medical conditions had mortality rates, disease-specific outcomes, and patient and caregiver satisfaction that were either improved or no different compared with inpatient admission. For observation units, several acute medical conditions were found to have no difference in mortality, a decreased length of stay, and improved patient satisfaction compared to inpatient admission; results for some conditions were more limited. Across all alternative management strategies, cost data were heterogeneous but showed near-universal savings when assessed.CONCLUSIONS AND RELEVANCE For low-risk patients with a range of acute medical conditions, evidence suggests that alternative management strategies to inpatient care can achieve comparable clinical outcomes and patient satisfaction at lower costs. Further study and application of such opportunities for health system redesign is warranted.