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To compare the effects of intravenous fentanyl and lidocaine on hemodynamic changes following endotracheal intubation in patients requiring Rapid Sequence Intubation (RSI) in the emergency department (ED).A single-centered, prospective, simple non-randomized, double-blind clinical trial was conducted on 96 patients who needed RSI in Edalatian ED. They were randomly divided into three groups (fentanyl group (F), lidocaine group (L), and fentanyl plus lidocaine (M) as our control group). M was administered with 3 μgr/kg intravenous fentanyl and 1.5 μgr/kg intravenous lidocaine, F was injected with 3 g/kg intravenous fentanyl and L received 1.5 mg/kg intravenous lidocaine prior to endotracheal intubation. Heart rate (HR) and mean arterial pressure (MAP) were assessed four times with the chi-square test: before, immediately after, 5 and 10 min after intubation. Intervention was discontinued for five people due to unsuccessful CPR.HR was notably different in F, L and M groups during four time courses (p < 0.05). Comparison of MAP at measured points in all groups exhibited no significant difference (p > 0.05). In fentanyl group both HR and MAP increased immediately after intubation, and significantly decreased 10 min after intubation (p < 0.05).Overall, the result of this study shows that lidocaine effectively prevents MAP and HR fluctuations following the endotracheal intubation. According to our findings, lidocaine or the combination of fentanyl and lidocaine are able to diminish hemodynamic changes and maintain the baseline conditions of the patient, thus could act more effectively than fentanyl alone.