Objective:To compare the efficacy, safety, and cost of continuous infusions of lorazepam, midazolam, and propofol in a critically ill trauma/surgery patient population.Design:A prospective, randomized, nonblinded, single center.Setting:A 16-bed intensive care unit.Patients:A total of 30 ventilated patients who were 18-70 yrs of age and required pharmacologic sedation. Patients with renal and/or liver failure, a history of alcohol abuse, a head injury, or in a coma were excluded.Interventions:Patients were randomized by block design to receive lorazepam, midazolam, or propofol. Initial boluses and infusion rates were as follows: lorazepam 0.05 mg/kg, then 0.007 mg/kg/hr; midazolam 0.05 mg/kg, then 0.003 mg/kg/hr; and propofol 0.25 mg/kg, then 0.06 mg/kg/hr. Sedation was assessed and agents titrated every 5-10 mins to achieve ≥2 and <5 on the modified Ramsay scale. Once adequate response was achieved, agents were titrated to maintain the desired level of sedation.Measurements and Main Results:Maintenance doses of lorazepam 0.02 ± 0.01 mg/kg/hr, midazolam 0.04 ± 0.03 mg/kg/hr, and propofol 2.0 ± 1.5 mg/kg/hr achieved the desired level of sedation 68%, 79%, and 62% of the time, respectively. Oversedation occurred most often with lorazepam, compared with midazolam and propofol, at 14%, 6%, and 7% of the assessment times, respectively. Undersedation occurred most frequently with propofol compared with lorazepam and midazolam, at 31%, 18%, and 16% of the assessment times, respectively.The mean number of dosage changes per day was 7.8 ± 4.3 for lorazepam, 4.4 ± 2.9 for midazolam, and 5.6 ± 6.0 for propofol (p= .91). Sedation costs per patient day (mean ± SD) were $48 ± $76 (lorazepam), $182 ± $98 (midazolam), and $273 ± $200 (propofol) (p= .005). The potential savings, if all study patients had received lorazepam, is $14,208 compared with $8,808 if all received midazolam.Conclusions:The data suggest that lorazepam appears to be a cost-effective choice for sedation; however, oversedation may be problematic. Midazolam is the most titratable drug in our population, avoiding excessive oversedation or undersedation. Trauma patients may respond inadequately to propofol even at higher doses. Lorazepam may be the sedative of choice in critically ill trauma/surgery patients.