BACKGROUND: Patients' comprehension of their medical conditions is fundamental to patient-centered care. Hospitalizations present opportunities to educate patients but also challenges to patient comprehension given the complexity and rapid pace of clinical care. We conducted a systematic review of the literature to characterize the current state of inpatients' knowledge of their hospitalization, assess the methods used to determine patient comprehension, and appraise the effects of interventions on improving knowledge. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for articles published from January 1, 1995 through December 11, 2017. Eligible studies included patients under inpatient or observation status on internal medicine, family medicine, or neurology services. We extracted study characteristics (author, year, country, study design, sample size, patient characteristics, methods, intervention, primary endpoints, results) in a standardized fashion. The quality of observational studies was assessed using the NIH Quality Assessment Tool for Observation Cohort and Cross-Sectional Studies and the quality of interventional studies was assessed using adapted EPOC criteria from the Cochrane Collaboration. RESULTS: Twenty-eight studies met the criteria for inclusion, including 17 observational studies and 11 interventional studies. Patient knowledge of all aspects of their hospitalization was poor and patients often overestimated their knowledge. Older patients and those with lower education levels were more likely to have poorer knowledge. Intervention methods varied, but generally showed improvements in patient knowledge. Few interventional studies assessed the effect on health behaviors or outcomes and those that did were often underpowered. DISCUSSION: Clinicians should be aware that comprehension is often poor among hospitalized patients, especially in those with lower education and advanced age. Our results are limited by overall poor quality of interventional studies. Future research should use objective, standardized measures of patient comprehension and interventions should be multifaceted in approach, focusing on knowledge improvement while also addressing other factors influencing outcomes.knowledge and health behaviors (e.g., medication adherence) and clinical outcomes (e.g., hospital readmission), though this was not the primary aim of the review.A medical librarian (J.P.), with training in systematic review methodology, searched MEDLINE, EMBASE, and the Cochrane Library for articles published from January 1, 1995 through December 11, 2017. The following subject terms and keywords were used: inpatients, knowledge, comprehension, hospitalization, patient discharge, discharge planning, and goals of patient care (Appendixes 1, 2, and 3). We limited results to English language publications of randomized controlled trials, prospective analyses, retrospective analyses, case control, cohort, cross-sectional, and non-controlled before-and-after studies that were published in peer-reviewed journal...