Background: Some patients with respiratory failure who are in need of mechanical ventilation require sedation to tolerate the inserted endotracheal tube (ETT) and other unpleasant stimuli. While a light sedation is satisfactory, deep sedation can interfere with the weaning process of patient from mechanical ventilator. Nevertheless, so far, the ideal regimen for sedatives and analgesics has not been found. We evaluate the effect of intratracheal administration of lidocaine for sedation of patients under mechanical ventilation. Methods: In a double-blind randomized clinical trial, 50 patients aged 33–65 years who had no obvious brain injury, in need of mechanical ventilation were enrolled into this study. They were randomized into two groups; the treatment group received 2.5 mL of 2% lidocaine, and the control group received 2.5 mL of normal saline via ETT each two hours for 12 h under sterile conditions. The baseline sedation was maintained with morphine, midazolam, or both, which were titrated to patient comfort and to maintain an optimum sedation score throughout the entire study. Results: During 12 h of the study, the mean±SD total morphine and midazolam requirements were 7.13±0.96 and 4.65±1.15 mg, respectively, in the treatment group, and 11.08±0.77 and 6.37±1.17 mg, respectively, in the control group. There was a significant (P<0.05) reduction in the requirements for both drugs during the study in the treatment group as compared to the control group. Conclusion: Intratracheal administration of lidocaine significantly reduces sedative requirements in intubated patients during 12 h. In the short-term, no side effects or complications were observed.