Background Desflurane is an excellent but expensive volatile anesthetic agent. Dexmedetomidine and propofol may decrease intraoperative desflurane consumption. This study aimed to compare the desflurane-sparing effect of dexmedetomidine and propofol in patients undergoing laparoscopic surgeries under bispectral index (BIS)-guided general anesthesia (GA). Methods Sixty-two adult patients, ASA (American Society of Anesthesiologists) physical status I or II, of either sex, aged between 18 and 60 years, were randomly allocated into group D or group P. Only group D patients received an intravenous (IV) bolus of dexmedetomidine (1 mcg/kg) over 15 minutes before induction. In both groups, GA was induced following the standard protocol with propofol infusion (0.5 mg/kg/min) until the BIS value dropped below 60. For maintenance, group D and group P patients received IV dexmedetomidine infusion (0.5 mcg/kg/h) and propofol infusion (50 mcg/kg/min), respectively. In both groups, desflurane dial concentration was adjusted between 3 and 8% to maintain the BIS within the range of 45-55. An hourly bolus of IV fentanyl (0.5 mcg/kg) and a half-hourly bolus of IV vecuronium (0.02 mg/kg) were administered. The total amount of desflurane consumed, duration of pneumoperitoneum, extra aliquots of propofol used during maintenance, number of boluses of IV atropine, fentanyl, and esmolol, time to attain Ramsay Sedation Score of 2 after extubation, time to first postoperative analgesic request at Numerical Rating Scale (NRS) score ≥ 4, time to reach a Modified Aldrete Score of ≥9, and incidence of any side effects were recorded. All the data were analyzed and compared using appropriate statistical tests, and a p-value of <0.05 was considered significant. Results The final data analysis was performed on 60 patients. The mean desflurane consumption was clinically higher in group P patients than in group D, but the difference was statistically insignificant (p-value > 0.05). The mean induction dose of propofol was significantly less in group D than in group P (p-value < 0.05). After extubation, the difference in time to the first analgesic request (NRS ≥ 4) between the groups was statistically significant (p-value < 0.05). Group D patients had a residual intraoperative analgesic effect. Conclusion The effects of dexmedetomidine and propofol infusions on desflurane consumption in laparoscopic surgeries are comparable, with minimal effects on intraoperative hemodynamics and postoperative recovery profiles., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Sri Venkateswara Institute of Medical Sciences Institutional Ethics Committee, Tirupati issued approval Roc.No.AS. 11/IEC/SVIMS/2017. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Machani RamaMurthy et al.)