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Although known to be an independent predictor of poor outcomes in medical intensive care unit (ICU) patients, limited data exist regarding the prevalence of and risk factors for delirium among surgical (SICU) and trauma ICU (TICU) patients. The purpose of this study was to analyze the prevalence of and risk factors for delirium in surgical and trauma ICU patients.SICU and TICU patients requiring mechanical ventilation (MV) >24 hours were prospectively evaluated for delirium using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). Those with baseline dementia, intracranial injury, or ischemic/hemorrhagic strokes that would confound the evaluation of delirium were excluded. Markov models were used to analyze predictors for daily transition to delirium.One hundred patients (46 SICU and 54 TICU) were enrolled. Prevalence of delirium was 73% in the SICU and 67% in the TICU. Multivariable analyses identified midazolam [OR 2.75 (CI 1.43–5.26, p = 0.002)] exposure as the strongest independent risk factor for transitioning to delirium. Opiate exposure showed an inconsistent message such that fentanyl was a risk factor for delirium in the SICU (p = 0.007) but not in the TICU (p = 0.936), whereas morphine exposure was associated with a lower risk of delirium (SICU, p = 0.069; TICU p = 0.024).Approximately 7 of 10 SICU and TICU patients experience delirium. In keeping with other recent data on benzodiazepines, exposure to midazolam is an independent and potentially modifiable risk factor for the transitioning to delirium.