Background: Various drugs have been used as premedication in pediatric anesthesia practice. Clonidine, alpha-2 agonist has entered anesthesia practice and its efficacy as an oral premedication drug is to be evaluated. Aim: The aim of this study is to evaluate and compare the clinical effects of oral midazolam and oral clonidine as premedication in children with regard to drug acceptance, pre-operative sedation, anxiolysis, acceptance of mask for induction of anesthesia, intravenous (IV) cannulation, and recovery profile. Materials and Methods: A prospective randomized, double-blind comparative study in children, ASA physical Status I in the age group of 1-10 years, posted for elective lower abdominal surgeries (duration 30-45 min) was done. Patients were randomized into two groups, Group C and Group M of 50 each. Patients in Group C received powdered clonidine tablet (100 mu g) dissolved in 100 ml of water in the dose of 4 mu g/kg, 45 min before surgery. Patients in Group M received preservative free parenteral form of midazolam in the strength of 5 mg/ml in the dose of 0.5 mg/kg 45 min before surgery. Results: All the children accepted the drugs very well without spitting (or) vomiting. 90% of patients in clonidine group have sedation scores of 2 and 3 when compared with midazolam group, 54% respectively. Anxiety level on separation from parents was high with midazolam group. Level of mask acceptance, response to IV cannulation was better with clonidine group. The post-operative agitation is higher with midazolam group compared to clonidine group. Conclusion: Clonidine is a better oral premedicant drug in children producing higher sedation, decreased anxiety, improved mask acceptance and response to IV cannulation and diminished post-operative agitation.