STUDY OBJECTIVE To determine whether the use of continuous i.v. sedation is associated with prolongation of the duration of mechanical ventilation. DESIGN Prospective observational cohort study. SETTING The medical ICU of Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. PATIENTS Two hundred forty-two consecutive ICU patients requiring mechanical ventilation. INTERVENTIONS Patient surveillance and data collection. MEASUREMENTS AND RESULTS The primary outcome measure was the duration of mechanical ventilation. Secondary outcome measures included ICU and hospital lengths of stay, hospital mortality, and acquired organ system derangements. A total of 93 (38.4%) mechanically ventilated patients received continuous i.v. sedation while 149 (61.6%) patients received either bolus administration of i.v. sedation (n=64) or no i.v. sedation (n=85) following intubation. The duration of mechanical ventilation was significantly longer for patients receiving continuous i.v. sedation compared with patients not receiving continuous i.v. sedation (185+/-190 h vs 55.6+/-75.6 h; p<0.001). Similarly, the lengths of intensive care (13.5+/-33.7 days vs 4.8+/-4.1 days; p<0.001) and hospitalization (21.0+/-25.1 days vs 12.8+/-14.1 days; p<0.001) were statistically longer among patients receiving continuous i.v. sedation. Multiple linear regression analysis, adjusting for age, gender, severity of illness, mortality, indication for mechanical ventilation, use of chemical paralysis, presence of a tracheostomy, and the number of acquired organ system derangements, found the adjusted duration of mechanical ventilation to be significantly longer for patients receiving continuous i.v. sedation compared with patients who did not receive continuous i.v. sedation (148 h [95% confidence interval: 121, 175 h] vs 78.7 h [95% confidence interval: 68.9, 88.6 h]; p<0.001). CONCLUSION We conclude from these preliminary observational data that the use of continuous i.v. sedation may be associated with the prolongation of mechanical ventilation. This study suggests that strategies targeted at reducing the use of continuous i.v. sedation could shorten the duration of mechanical ventilation for some patients. Prospective randomized clinical trials, using well-designed sedation guidelines and protocols, are required to determine whether patient-specific outcomes (eg, duration of mechanical ventilation, patient comfort) can be improved compared with conventional sedation practices.