Background: Emergence agitation (EA) in children is increased after sevoflurane anesthesia. Nalbuphine and midazolam have been used for prophylactic treatment. It is characterized by mental confusion, irritability, disorientation, crying, and increased recovery time in the post anesthesia recovery room, increasing parents' concern and anxiety with respect to the clinical condition of their children. It can also lead to possible injury, damage to surgical dressings, lost intravenous catheters, and disconnected cables and monitoring instruments and source of dissatisfaction for parents, nurses, and others taking care of these children. Objectives: The aim of the present study was to compare the effect of nalbuphine and midazolam before termination of sevoflurane-based anesthesia on the incidence and severity of EA in children as a primary outcome and post-operative pain, comparison of alertness and spontaneous behavior according to 3 step scales, adverse effects in both groups, and intraoperative hemodynamics as a secondary outcome. Patients and Methods: This prospective double-blind randomized studyon 90 children between 4 and 8 years of age and of American Society of Anesthesiologists I undergoing adenotonsillectomy under sevoflurane-based anesthesia was enrolled in the study. Children were randomly allocated to one of the two equal groups: group (N) received nalbuphine 0.1 mg/kg and group (M) received midazolam 0.03 mg/kg. The study drugs were administered 5 min before the end of surgery. In the postanesthesia care unit, the incidence of EA was assessed with Aonos four-point scale. Severity of EA was assessed with the pediatric anesthesia emergence delirium scale upon admission (T0), after 5 min (T5), 10 min (T10), 15 min (T15), and 30 min (T30). Results: The incidence and severity of EA were lower in group (N) as compared with group (M) at T0, T5, and T10. Conclusion: Nalbuphine 0.1 mg/kg was more effective compared with midazolam 0.03 mg/kg in decreasing the incidence and severity of EA, when administered 5 min before the end of surgery in children undergoing adenotonsillectomy under sevoflurane anesthesia.