Objectives: To determine the incidence, severity, and preventability of and risk factors for medication-related harm (MRH) in community-dwelling older adults after hospital discharge. Design: Systematic review. Setting: A search of Medline, EMBASE, CINAHL, and the Cochrane Library was undertaken without time restrictions. Participants: Older adults (average age ≥65) participating in observational studies investigating postdischarge adverse drug reactions (ADRs) or adverse drug events (ADEs) within a defined follow-up period. Measurements: One author screened abstracts of all articles to exclude obviously irrelevant articles. Two authors independently screened the remaining articles for inclusion. Two authors independently extracted data, including study characteristics, MRH incidence, and risk factors; a third reviewer critically appraised and verified the data. Disagreements were resolved through discussion. Results: From 584 potentially relevant articles, 8 studies met our inclusion criteria: 5 North American and 3 European. Most of the included studies were of moderate quality. There was a wide range in MRH incidence, from 0.4% to 51.2% of participants, and 35% to 59% of MRH was preventable. MRH incidence within 30 days after discharge ranged from 167 to 500 events per 1,000 individuals discharged (17-51% of individuals). There is substantial methodological heterogeneity across multiple domains of the studies, including ADR and ADE definitions, characteristics of recruited populations, follow-up duration after discharge, and data collection. Conclusion: MRH is common after hospital discharge in older adults, but methodological inconsistencies between studies and a paucity of data on risk factors limits clear understanding of the epidemiology. There is a need for international consensus on conducting and reporting MRH studies. Data from large, multicenter studies examining a range of biopsychosocial risk factors could provide insight into this important area of safety. © 2018 American Geriatrics Society and Wiley Periodicals, Inc.