Background: The pre-operative period is a very stressful event for most of the individuals undergoing surgery especially the pediatric patients. So, relieving their pre-operative anxiety becomes an important concern for an anesthesiologist. Many anesthetic pre-medications are used to relieve this stress response. Of these pre-medications, midazolam and dexmedetomidine are effectively used as sedatives. The present study was planned to compare intranasal dexmedetomidine with intranasal midazolam as a pre-anesthetic medication in children. Forty-eight children aged 3-7 years, of either sex, weighing 13-22 kg, with American Society of Anesthesiologists (ASA) physical status 1 and undergoing elective adenotonsillectomy surgery were enrolled in this comparative prospective, double blinded, randomized clinical study. The children were divided into 2 groups: group D and group M, of 24 each. Forty-five minutes before induction of anesthesia, group D (n= 24) received intranasal dexmedetomidine at a dose of 1 mu g/kg and group M (n= 24) received intranasal midazolam of 0.2 mg/kg. Results: Children who were pre-medicated with dexmedetomidine had lower sedation scores, lower anxiety levels, easier child-parent separation, better mask acceptance, and lower pain scores than those who received midazolam. The incidence of emergence agitation was decreased in both groups with no significant difference. Conclusion: Intranasal dexmedetomidine seems to offer some advantages compared with midazolam. Thus, it can be used effectively and safely as a pre-anesthetic medication in children undergoing any surgical procedures under general anesthesia.