Increasing pressure on limited healthcare resources has necessitated the development of measures promoting early discharge and avoiding inappropriate hospital (re)admission. This systematic review examines the evidence for interventions in acute hospitals including (i) hospital-patient discharge to home, community services or other settings, (ii) hospital discharge to another care setting, and (iii) reduction or prevention of inappropriate hospital (re)admissions. Academic electronic databases were searched from 2005 to 2018. In total, ninety-four eligible papers were included. Interventions were categorized into: (1) pre-discharge exclusively delivered in the acute care hospital, (2) pre- and post-discharge delivered by acute care hospital, (3) post-discharge delivered at home and (4) delivered only in a post-acute facility. Mixed results were found regarding the effectiveness of many types of interventions. Interventions exclusively delivered in the acute hospital pre-discharge and those involving education were most common but their effectiveness was limited in avoiding (re)admission. Successful pre- and post-discharge interventions focused on multidisciplinary approaches. Post-discharge interventions exclusively delivered at home reduced hospital stay and contributed to patient satisfaction. Existing systematic reviews on tele-health and long-term care interventions suggest insufficient evidence for admission avoidance. The most effective interventions to avoid inappropriate re-admission to hospital and promote early discharge included integrated systems between hospital and the community care, multidisciplinary service provision, individualization of services, discharge planning initiated in hospital and specialist follow-up.