Background: Anxiety in children undergoing surgery was considered challenging situation for anesthesia. The intranasal dexmedetomidine and intranasal midazolam as preoperative sedation drugs are used. Objective: The aim of the current work was to evaluate and compare intranasal dexmedetomidine versus midazolam as premedication in pediatric anesthesia according to sedation scale, anxiety scale, child - parent separation scale, and mask accepting scale, heart rate, blood pressure, oxygen saturation and respiratory rate. Patients and methods: The study was carried out on 90 children, 2 to 6 years old, who underwnt day surgical procedures at Zagazig Univerisity Hospital. They were randomly assigned into three equal groups, all were given the study drug intranasally diluted in 1 ml NS. C-Group given 1 ml NS, D-group given 2ug/kg dexmedetomidine, and M-group given 0.3mg/kg midazolam. The groups were compared rgarding onset and degree of sedation, child parent separation scale, mask acceptance scale, hemodynamic parameters, and postoperative analgesic requirements. Results: The three groups were comparable with respect to basic demographic data. D - group showed higher alert sedation scale compared to M - group and C - group from 10 min intraoperative. Anxiety scale was significantly higher in C - group in comparison to other groups from 20 min intraoperative. Child parent separation scale was significantly lower in M - group in comparison to M - group and C - group. The median mask acceptance scale was significantly lower in D - group in comparison to M - group and C group. Conclusions: Intranasal dexmedetomidine 2 μg/kg could be used effectively and safely as a pre-anesthetic medication in children undergoing day case surgery compared to Intranasal midazolam 0.3 mg/kg.