To determine whether oral clonidine reduces pain on jnjection of propofol to lidocaine as compare to oral diazepam. A prospective, randomized double-blind clinical study was conducted in 200 elective patients scheduled for surgery under general anesthesia. There were randomized into 2 groups. The clonidine group (100 patients) took 300 µg of clonidine whereas the diazepam group (100 patients) had 10 mg of diazepam orally 120 minutes before surgery. An intravenous catheter No. 18 was inserted on the dorsum of hands in all patients. Anesthesia was induced by propofol with lidocaine (lidocaine : propofol = 1 : 10) : 2 mg/kg at rate of 0.2 ml/s. Visual analogue scale (VAS) pain scores were assessed in increments from 0-10 every 15 seconds until the patients were asleep. Vecuronium 0.1 mg/kg intravenously was administered for endotracheal intubation and maintenance with morphine 0.1 mg/kg intravenously, halothane 0.5-1.5% and N2O/O2. The mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgery. The results showed the incidence of moderate to severe VAS pain scores in the clonidine group (46%) were significantly lower than that in the diazepam group (63%) (P = 0.016). There was no statistically significant difference in the sedation score between the 2 groups. The MAP and HR in the clonidine group were significantly lower than that in the diazepam group (P < 0.001). The incidence of hypotension in the clonidine group was 17%, significantly higher than that in the diazepam group (P = 0.015). There was no statistically significant difference in the incidence of bradycardia between the 2 groups. We concluded that 5.6 µg/kg of oral clonidine significantly reduced pain on injection of propofol with lidocaine as compare to oral diazepam 0.2 mg/kg.