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To determine the costs associated with delirium in mechanically ventilated medical intensive care unit patients.Prospective cohort study.A tertiary care academic hospital.Patients were 275 consecutive mechanically ventilated medical intensive care unit patients.We prospectively examined patients for delirium using the Confusion Assessment Method for the Intensive Care Unit.Delirium was categorized as “ever vs. never” and by a cumulative delirium severity index. Costs were determined from individual ledger-level patient charges using cost-center-specific cost-to-charge ratios and were reported in year 2001 U.S. dollars. Fifty-one of 275 patients (18.5%) had persistent coma and died in the hospital and were excluded from further analysis. Of the remaining 224 patients, delirium developed in 183 (81.7%) and lasted a median of 2.1 (interquartile range, 1–3) days. Baseline demographics were similar between those with and without delirium. Intensive care unit costs (median, interquartile range) were significantly higher for those with at least one episode of delirium ($22,346, $15,083–$35,521) vs. those with no delirium ($13,332, $8,837–$21,471, p < .001). Total hospital costs were also higher in those who developed delirium ($41,836, $22,782–$68,134 vs. $27,106, $13,875–$37,419, p = .002). Higher severity and duration of delirium were associated with incrementally greater costs (all p < .001). After adjustment for age, comorbidity, severity of illness, degree of organ dysfunction, nosocomial infection, hospital mortality, and other potential confounders, delirium was associated with 39% higher intensive care unit (95% confidence interval, 12–72%) and 31% higher hospital (95% confidence interval, 1–70%) costs.Delirium is a common clinical event in mechanically ventilated medical intensive care unit patients and is associated with significantly higher intensive care unit and hospital costs. Future efforts to prevent or treat intensive care unit delirium have the potential to improve patient outcomes and reduce costs of care.