BACKGROUND: Propofol has a high incidence of pain with intravenous injection, and different methods have been used to minimize the incidence and severity of this pain. In this study, we have compared the effect of lidocaine pretreatment with that of ketamine pretreatment on propofol injection pain. METHODS: Ninety healthy female patients scheduled for general anesthesia were randomly divided into three groups; saline group (n=30), lidocaine group (n=30) and ketamine group (n=30). Each patient received 2 ml of pretreatment solution (normal saline, 1% lidocaine, 0.5% ketamine) via 18G angiocatheter inserted in the antecubital fossa after applying an arm tourniquet inflated to 50 mmHg. The tourniquet was released 1 minute later, followed by intravenous injection of 2.5 mg/kg of propofol. The assessment of pain was made at the induction of anesthesia and in the recovery room, and the severity of pain was classified as none, mild, moderate, severe by one observer. RESULTS: The severity and incidence of pain diminished significantly in the lidocaine group and the ketamine group compared with the saline group at the induction of anesthesia (p<0.05) and there was no significant difference between the lidocaine group and the ketamine group. We had similar results in the recovery room and one patient from the saline group and the ketamine group had no recall regarding injection pain. CONCLUSION: Intravenous ketamine pretreatment is as effective as intravenous lidocaine pretreatment in alleviating the propofol injection pain.