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Background and objectives: Awake fiberoptic intubation (AFOI) is usually performed in patients with an anticipated difficult airway. Various sedation regimens are used during AFOI, however, most of them cause respiratory depression. The present study aims to compare the effectiveness of fentanyl with ketamine versus dexmedetomidine in search of a better sedation regimen which would achieve desirable intubating conditions and hemodynamic stability without causing respiratory depression. Methods: This is a single centered randomized, double-blind clinical trial. Patients of both sexes between age 18–55 years and ASA (American Society of Anesthesiologists) physical status I–II with an anticipated difficult airway were randomly divided into two groups of thirty each. Group FK patients received intravenous fentanyl and ketamine, and group DX patients received dexmedetomidine, until Ramsay sedation scale ≥ 2. Heart rate (HR), mean blood pressure (MBP), oxygen saturation (SpO2), respiratory rate (RR), endoscopy time, intubation time, first end-tidal carbon dioxide (ETCO2) after intubation, endoscopist satisfaction score, and patient discomfort score were recorded during the study period. The level of recall was assessed on the next postoperative day. Results: Endoscopist satisfaction score was better in group DX patients (p |