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Background: In 2020, there were 36.7 million reported falls among older adults (65+) in the United States. Ethanol and other sedating substances may increase fall risk among older adults due to their effect on cognitive and physical function. We estimate the prevalence of these substances in blood specimens of older adults presenting with a fall injury at selected trauma centers. Methods: The initial study collected blood specimens from May 2020 through July 2021 from adults undergoing a trauma team evaluation at selected United States Level 1 trauma centers. We limited our study to older adults evaluated after a fall (n = 1,365) and selected a random sample (n = 300) based on age, sex, and trauma-center quotas. Medical health records and blood specimens obtained at trauma center presentation were analyzed. We estimated the prevalence of ethanol, benzodiazepines, cannabinoids, and opioids in the blood specimens. Two-sample tests of binomial proportions and Chi-square two-tailed tests were used to compare prevalence estimates of substances by demographic characteristics. Results: At least one substance was detected among 31.3% of samples analyzed. Prevalences of specific substances detected were 9.3% (95% CI: 6.0–12.6%) for benzodiazepines, 4.3% (95% CI: 2.0–6.7%) for cannabinoids, 8.0% (95% CI: 5.2–11.7%) for ethanol, and 15.0% (95% CI: 10.9–19.1%) for opioids. There were 18 deaths (6%; 95% CI: 3.6–9.3%). One-third of decedents had at least one substance detected in their blood. Discussion: Opioids were the most frequently detected substance, followed by benzodiazepines, ethanol, and cannabinoids. Substance use prevalence was not uniform across demographics, with differences observed by sex and age. Conclusions: This study provides insight into the frequency of the presence of substances that may contribute to fall risk and serious injury among older adults. Screening older adults for substances that impair cognitive and physical function can enhance clinical fall prevention efforts. [ABSTRACT FROM AUTHOR]