OBJECTIVE: To compare anxiolysis produced by intranasal clonidine with intranasal midazolam as premedication in children undergoing surgery. DESIGN: Double-blind randomized controlled study. SETTING: Tertiary-care hospital, July 2009 to June 2010. PATIENTS: 60 American Society of Anesthesiologists physical status I-II surgical patients aged 1-10 yr. INTERVENTION: Participants randomly allocated to receive either intranasal clonidine 4 mcg/kg (Group I) with atropine or intranasal midazolam 0.3 mg/kg (Group II). OUTCOME MEASURES: Primary: satisfactory anxiolysis at 30 min after drug administration. Secondary: satisfactory mask acceptance, times of onset of sedation and anxiolysis, drug acceptance, level of sedation, wake-up score and side effects. RESULTS: All children achieved satisfactory anxiolysis at 30 min. Group I fared significantly better than GroupII on mask acceptance (100% in Group I vs. 80% in Group II; P=0.024), drug acceptance (93% vs. 13%; P<0.001) and proportion of patients with satisfactory wake up scores (100% vs. 53%; P<0.001). Group II patients had significantly faster onset of sedation (median 10 min vs. 15 min; P<0.05) but not that of anxiolysis compared to Group-I (median 10 min for both groups; P>0.05). Side effects were significantly more frequent in Group II. CONCLUSIONS: Though intranasal midazolam produced faster sedation, both the drugs produced satisfactory anxiolysis at 30 min.