Abstract Background Ultrasound-guided transversus abdominis plane (TAP) block became a common analgesic method after surgery involving the abdominal wall. Different adjuvants have been used to intensify the quality and the duration of local anesthetics. Aim of the Work to compare dexmedetomidine versus dexamethasone added to bupivacaine as adjuvant to the local anesthetic bupivacaine during Ultrasoundguided transversus abdominis plane (TAP) block for postoperative analgesia in laparoscopic cholecystectomy, characteristics including duration of postoperative analgesia, post-operative pain score and sedation score. Patients and Methods The current study included 40 patients scheduled for elective laparoscopic cholecystectomy surgery were given Ultrasound-guided transversus abdominis plane (TAP) block after induction of general anesthesia. The patients were randomly allocated into two groups. Group (DM): patients received 22 ml of Bupivacaine 0.25 %in 20 ml + 1 ug/kg of dexmedetomidine in 2 ml on both sides. Group (DS): patients received 22 ml of Bupivacaine 0.25 % in 20 ml + 4 mg of dexamethasone in 2 ml on both sides. Results VAS pain score at rest especially 6, 12, 24, 48 hrs is significantly less in dexmedetomidine group than in dexamethasone group. VAS pain score at movement especially 6, 12, 24, 48 hrs is significantly less in dexmedetomidine group than in dexamethasone group. 1st rescue dose of analgesics was delayed up to (19.76±2.51 hrs), in dexmedetomidine group in comparison to (12.92±2.17 hrs) in dexamethasone group. The total dose of paracetamol required by patients in the dexmedetomidine group was (3.18±1.07 gm) compared to (5.33±1.16 gm) in dexamethasone group, indicating longer pain-free period and less requirement of analgesia in the dexmedetomidine group. Therefore, use of dexmedetomidine in TAP block has a beneficial effect in reducing the dose of systemic analgesic requirements. Conclusion co administration of 1 ug/kg of dexmedetomidine vs dexamethasone 4 mg to 0.25 % bupivacaine on both sides by US guided TAP block leaded to significant changes in the form of lower HR at 12, 24, 48 hrs, lower sedation score at 1, 6, 12, 24, 48 hrs and no significant changes in systolic blood pressure, diastolic blood pressure, oxygen saturation and respiratory rate.