IMPORTANCE: Reducing early (<30 days) hospital readmissions is a policy priority aimed at improving health care quality. The cumulative complexity model conceptualizes patient context. It predicts that highly supportive discharge interventions will enhance patient capacity to enact burdensome self-care and avoid readmissions. OBJECTIVE: To synthesize the evidence of the efficacy of interventions to reduce early hospital readmissions and identify intervention features-including their impact on treatment burden and on patients' capacity to enact postdischarge self-care-that might explain their varying effects. DATA SOURCES: We searched PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus (1990 until April 1, 2013), contacted experts, and reviewed bibliographies. STUDY SELECTION: Randomized trials that assessed the effect of interventions on all-cause or unplanned readmissions within 30 days of discharge in adult patients hospitalized for a medical or surgical cause for more than 24 hours and discharged to home. DATA EXTRACTION AND SYNTHESIS: Reviewer pairs extracted trial characteristics and used an activity-based coding strategy to characterize the interventions; fidelity was confirmed with authors. Blinded to trial outcomes, reviewers noted the extent to which interventions placed additional work on patients after discharge or supported their capacity for self-care in accordance with the cumulative complexity model. MAIN OUTCOMES AND MEASURES: Relative risk of all-cause or unplanned readmission with or without out-of-hospital deaths at 30 days postdischarge. RESULTS: In 42 trials, the tested interventions prevented early readmissions (pooled random-effects relative risk, 0.82 [95%CI, 0.73-0.91]; P < .001; I2 = 31%), a finding that was consistent across patient subgroups. Trials published before 2002 reported interventions that were 1.6 times more effective than those tested later (interaction P = .01). In exploratory subgroup analyses, interventions with many components (interaction P = .001), involving more individuals in care delivery (interaction P = .05), and supporting patient capacity for self-care (interaction P = .04) were 1.4, 1.3, and 1.3 times more effective than other interventions, respectively. A post hoc regression model showed incremental value in providing comprehensive, postdischarge support to patients and caregivers. CONCLUSIONS AND RELEVANCE: Tested interventions are effective at reducing readmissions, but more effective interventions are complex and support patient capacity for self-care. Interventions tested more recently are less effective. Copyright 2014 American Medical Association. All rights reserved.