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Background: Anesthesia for endoscopic retrograde cholangiopancreatography poses many challenges. The level of sedation is highly unpredictable and can shift from conscious to deep sedation with the loss of protective reflexes. Propofol, which is a popular drug, has a narrow therapeutic index. We study the effect of intranasal dexmedetomidine on propofol and fentanyl consumption. Materials and Methods: Ninety patients were randomly divided into two groups to receive either intranasal 1.5 µg/kg dexmedetomidine or saline. After 1 h, the procedure was commenced. Propofol and fentanyl were used to conduct anesthesia. The primary outcome was intraoperative propofol and fentanyl consumption. The secondary outcome was preprocedural hemodynamic parameter and sedation score. Results: There was no statistically significant difference found in terms of demographic data (age, sex, height, weight, or BMI), duration of procedure, basal hemodynamic parameters, and sedation scale. There was a significant reduction in propofol (227.11 ± 61.27 mg vs. 146.89 ± 31.25 mg) and fentanyl (98.11 ± 13.95 µg vs. 82.44 ± 13.34 µg) consumption in the dexmedetomidine group. There was a significant reduction in pulse rate (95.13 ± 11.00 vs. 82.89 ± 9.45) and mean arterial pressure (98.27 ± 6.40 vs. 91.44 ± 8.02) at 60 min in the dexmedetomidine group. The preprocedural sedation score was statistically significantly reduced in the dexmedetomidine group (4.80 ± 0.40 vs. 3.67 ± 0.48). Conclusion: Intranasal administration of 1.5 µg/kg dexmedetomidine can reduce perioperative anesthetic drug requirements. It provides better preprocedural sedation score and hemodynamic profile. [ABSTRACT FROM AUTHOR]