Background: Intranasal midazolam is a novel technique for administering premedication in children. It has been shown to be more effective than parental presence or placebo in reducing anxiety and improving patient’s compliance at induction of anesthesia. Dexmedetomidine is selective 2 agonist with sedative, anxiolytic and analgesic properties with favorable pharmacokinetics. We designed this prospective randomized double-blinded study to compare the safety and efficacy of midazolam and dexmedetomidine administered intranasally as premedication in children undergoing cardiac surgery for CHD. Method: Sixty-two children belonging to the American Society of Anaesthesiologists (ASA) class I and II, scheduled for elective cardiac surgery were divided into two groups by standard randomization technique. Patients belonging to group M received intranasal midazolam 0.2 mg/kg whereas patients in group D received intranasal dexmedetomidine 1 µgm/kg 30 min prior to surgery in an adequately monitored condition. Patient’s sedation score, behaviour scores, attitude, heart rate, respiratory rate, oxygen saturation, intravenous cannula acceptance and face mask acceptance at the time of induction were studied by an observer till induction of anesthesia. Results: There was no significant difference in sedation score in both the groups except at 20 minutes, when it was significantly lower in patients belonging to Group D as compared to those of Group M. There was no significant difference inheart rate, respiratory rate, SpO2, behavior score, parental separation acceptance, behavior at separation and level of sedation atinduction of anaesthesia between the two groups. There was a significant difference in the number of patients with a change of behaviour (6.4% v/s 34.4%) and change of sedation (7.1% v/s 37.5%) in Group M and Group D respectively. Patients inGroup M were calmer and allowed face mask application at the time of induction of anesthesia. Conclusion: Intranasal route is safe and effective for administering both, midazolam and dexmedetomidine as premedication in children undergoing corrective surgery for congenital heart disease. However, we observed better behaviour with midazolam at induction of anesthesia.