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Purpose: Delirium risk assessment in the acute-care setting generally does not account for frailty. The objective of this retrospective study was to identify factors associated with delirium, considering the interdependency of clinical variables with frailty syndrome in complex older patients., Methods: The clinical records of 587 participants (248 M, median age 84) were reviewed, collecting clinical, anamnestic and pharmacological data. Frailty syndrome was assessed with the Clinical Frailty Scale (CFS). Delirium was the main study endpoint. The correlations of the considered anamnestic and clinical variables with delirium and its subtypes were investigated selecting only those variables not showing a high overlap with frailty. Correlations associated with a 25% excess of frequency of delirium in comparison with the average of the population were considered as statistically significant., Results: Delirium was detected in 117 (20%) participants. The presence of one among age > 85 years old, CFS > 4 and invasive devices explained 95% of delirium cases. The main factors maximizing delirium incidence at the individual level were dementia, other psychiatric illness, chronic antipsychotic treatment, and invasive devices. The coexistence of three of these parameters was associated with a peak frequency of delirium, ranging from 57 to 61%, mostly hypoactive forms., Conclusions: In acute-care wards, frailty exhibited a strong association with delirium during hospitalization, while at the individual level, dementia and the use of antipsychotics remained important risk factors. Modern clinical prediction tools for delirium should account for frailty syndrome., (© 2024. The Author(s).)