Background: ICU hospitalized patients usually need sedation. Common sedatives include benzodiazepines, opioids, barbiturates and etc. This study was conducted to compare the sedative, hemodynamic and respiratory effects of propofol and remifentanil in pulmonary disease patients requiring intubation and mechanical ventilation in intensive care unit of Masih Daneshvari Hospital during the years 2005-2007. Materials and Methods: This study was conducted as a randomized controlled clinical trial. All patients with pulmonary disease requiring mechanical ventilation in the ICU were randomly divided into two groups. The first group was given an initial 10 µg /kg/min infusion of propofol and the second group received an infusion of remifentanil starting with 0.05 µg /kg and the doses sequentially increased to reach a sedation state of 3-4 according to Ramsay sedation scale. The regimen was continued for 48 hours, during which blood pressure, heart rate, and respiratory rate were monitored every 3 hours. Data was analyzed using SPSS version 11 software. Results: A total of 40 patients with a mean age of 58.67±18.57yrs (range 21-85 yrs) including 27 (67.5%) males and 13 (32.5%) females entered the study. The mean time to optimal sedation was 17.9±13.9 min and 20.16 ±16.11 min for remifentanil and propofol groups, respectively (p=0.09). The mean systolic and diastolic blood pressures of each group showed a small decrease after initiation of infusion but this decrease was not statistically significant (p= 0.26 for remifentanil and p=0.12 for propofol group). The heart rate and respiratory rate showed no dramatic change during the infusion period. Conclusion: Both remifentanil and propofol are suitable drugs for sedating patients with pulmonary disease and neither of them induces dramatic hemodynamic changes. Therefore, using each of them is effective for optimal sedation of patients. (Tanaffos2010; 9(2): 54-60)