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Objectives: Abbreviations are often used in medicine yet may be a source of confusion for patients and their families. We aimed to determine the general public's understanding of commonly used medical acronyms., Methods: For this cross-sectional study, we surveyed state fair visitors regarding their understanding of 5 common medical acronyms. An electronic survey was administered to a volunteer sample of adults who spoke and read English and who had never trained to work in medicine or nursing. Free-text responses were coded as correct, partially correct, or incorrect by 2 independent researchers, adding a third researcher if consensus was not reached. Analysis methods included descriptive statistics, Fisher exact tests, and multivariable logistic regression models., Results: We recruited 204 volunteers (55% female; mean age 43 years; 67% had a bachelor's degree or higher). ED (emergency department) was correctly defined by 32%, PCP (primary care provider/physician) by 18%, CBC (complete blood count) by 14%, and PRN (as needed) and NPO (nothing by mouth) by 13% each. Female gender was associated with higher odds of correctly understanding NPO (odds ratio, 3.11; 95% confidence interval, 1.18-8.21; P = .02); older age was associated with higher odds of understanding PRN (odds ratio, 1.03; 95% confidence interval, 1.00-1.05; P = .04). Education level was not found to correlate significantly with successful explanation of any tested acronym., Conclusions: Medical acronyms are a predictable source of miscommunication. In this large cross-sectional study, none of the acronyms evaluated was understood correctly by more than one-third of adults. Clinicians should avoid using acronyms with patients and families to minimize confusion., (Copyright © 2023 by the American Academy of Pediatrics.)