Delirium affects 60 to 80% of ventilated patients and is associated with worse clinical outcomes including death. Unfortunately, there are limited data regarding the prevalence and risk factors of delirium in critically ill burn patients. The objectives of this study were to evaluate the prevalence of delirium in ventilated burn patients, using validated instruments, and to identify its risk factors. Adult ventilated burn patients at two tertiary centers were prospectively evaluated for delirium using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) for 30 days or until intensive care unit discharge. Patients with neurologic injuries, severe dementia, and those not expected to survive >24 hours were excluded. Markov logistic regression was used to identify the risk factors of delirium, adjusting for clinically relevant covariates. The 82 ventilated burn patients had a median (interquartile range) age of 48 (38-62) years, Acute Physiology and Chronic Health Evaluation II scores 27 (21-30), and percent burns of 20 (7-32). Prevalence of delirium was 77% with a median duration of 3 (1-6) days. Exposure to benzodiazepines was an independent risk factor for the development of delirium (odds ratio: 6.8 [confidence interval: 3.1-15], P < .001), whereas exposure to both intravenous opiates (0.5 [0.4-0.6], P < .001) and methadone (0.7 [0.5-0.9], P = .02) was associated with a lower risk of delirium. In conclusion, delirium occurred at least once in approximately 80% of ventilated burn patients. Exposure to benzodiazepines was an independent risk factor for delirium, whereas opiates and methadone reduced the risk of developing delirium, possibly through reduction of pain in these patients.