Background: Local anesthetic adjuvants prolong analgesia duration with single shot interfascial plane blocks.They potentiate the analgesic effect of the local anesthetics. These adjuvants include several groups and different mechanisms of action such as dexamethasone and dexmedetomidine. Objectives: This study was aimed at achievement of better analgesia for total abdominal hysterectomy patients via prolongation of sensory block duration and reducing opioid consumption. PatientsandMethods:This study was carried out at Zagazig University Hospitals where 84 female patients scheduled for total abdominal hysterectomy aged from 40 to 60 years, ASA physical status grade I, II and body mass index (BMI) 18.5-30 kg/m². Patients were classified into three groups (28 each), group C (received bilateral ESPB with 20 ml bupivacaine 0.25% plus 1ml saline), group O (received bilateral ESPB with 20 ml bupivacaine 0.25% plus 1ml dexamethasone (4mg)), group D (received bilateral ESPB with 20 ml bupivacaine 0.25% plus 1 ml dexmedetomidine (0.5ug/kg) in saline). They underwent history taking, general examination, laboratory investigations, preoperative erector spinae plane block (ESPB) and GA. Results: There was statistically significant difference between three groups regarding visual analog scale (VAS) and nalbuphine consumption where D group had better pain control than other groups. Conclusions: It could be concluded that dexmedetomidine as an adjuvant to 0.25% bupivacaine in ultrasound guided erector spinae plane block is more efficacious than dexamethasone in hastening the onset, prolonging sensory blockade, delaying the time for request of rescue analgesia, and decreasing total nalbuphine consumption.