OBJECTIVES: Medication Guides are patient-directed, Food and Drug Administration (FDA)-approved labeling intended to provide risk and safe-use information for prescription medications in easy-to-read, lay language. They were introduced to help patients understand and manage risks and maximize benefit from products by aiding in decision-making and helping improve adherence to and appropriate use of medications. This review was designed to assess whether patients are receiving medication guides per federal regulations and are able to use them as intended. METHODS: Knowledge, Attitudes, and Behavior (KAB) survey results in a heterogeneous sample of FDA-mandated REMS were reviewed to assess understanding of key risk messages (KRM) and receipt, reading, and understanding of medication guides. Results were calculated individually and compared across surveys. RESULTS: The review includes results from 36 patient KAB surveys for products in 8 therapeutic areas. Sample sizes ranged from 10-628 respondents per survey. Receipt: Median 89.3% (range 58.1-99.6%) of respondents reported receiving a medication guide. Reading: Median 93.1% (range 77.0-100.0%) of respondents reporting receiving a medication guide reported reading at least some of it. Understanding: Median 93.7% (range 36.8-100.0%) of respondents reported understanding all or most of what they read in the medication guide. Median 98.3% (range 64.6-100.0%) of respondents reported they understood all or most of what they read after having someone explain the information. In an objective assessment of understanding KRM of medication guides, median 72.4% (range 1.2-100.0%) of respondents answered questions correctly. CONCLUSIONS: This review demonstrates the inconsistency of usability of medication guides for the purposes intended as shown by the range of responses, particularly objective assessment of KRM understanding. Usability may be limited by incomplete distribution and inadequate risk communication.  Data will be presented to discuss differences in reported and demonstrated understanding and possible reasons why patients may be unable to use medication guides as they are intended.