Background: To evaluate whether using dexmedetomidine in conjunction with local anesthesia may prolong the period of pain relief after a vaginal hysterectomy and promote early mobility. Method: This research compared and analyzed the results of 60 patients (ASA I–II, 30–60 years old) who had general anesthesia during their operation. Subjects were allocated at random to receive either dexmedetomidine (Group RF) or fentanyl (Group RD) in combination with local anesthesia. Post-operative analgesic consumption, pain scores, and time to initial ambulation were documented for 24 hours. Results: Both groups had comparable baseline characteristics and hemodynamic stability. In group RF, the mean duration of analgesic medication use was considerably longer (4.93 ± 1.34 hours) compared to group RD (4.38 ± 1.43 hours), has 0.001 as the statistically significant p-value. Moreover, group RF had an earlier time to start ambulation. Conclusion: In a laparoscopic-assisted vaginal hysterectomy, dexmedetomidine, used as an adjuvant to local anesthesia, significantly prolongs post-operative analgesia and facilitates early ambulation compared to fentanyl, suggesting potential advantages. © 2024 Elsevier B.V., All rights reserved.