BACKGROUND: Propofol has a high incidence of pain with intravenous injection, and many different methods have been used to minimize the incidence and severity of this pain. In this study, we have compared the effect of saline pretreatment with that of lidocaine mixed with propofol after tramadol pretreatment on propofol injection pain. METHODS: Eighty patients scheduled for general anesthesia were randomly divided into four groups. Control group (n = 20) received 2 ml of 0.9% saline pretreatment, Group 1 (n = 20) received 50 mg of tramadol pretreatment, Group 2 (n = 20) received 40 mg of 2% lidocaine pretreatment and Group 3 (n = 20) received 40 mg of 2% lidocaine mixed with propofol after 50 mg of tramadol pretreatment. Each patient received one of the pretreatment drugs via 18 G angiocatheter inserted in the antecubital fossa after applying an arm tourniquet inflated to 70 mmHg. The tourniquet was released 1 minute later, followed intravenous injection of 2 mg/kg of propofol at a rate of 1 ml/sec. After 50 mg of propofol were injected, patients were assessed for pain score. The severity of pain was classified as 0, 1, 2, 3 (none, mild, moderate, severe) by one observer. RESULTS: The severity and incidence of pain were significantly reduced in group 2 and group 3 compared with control group for intravenous injection of propofol (P<0.05). but there was no significant difference between control group and group 1. CONCLUSIONS: Mixed administration of lidocaine-propofol after tramadol pretreatment could significantly reduce the severity and incidence of pain for intravenous injection of propofol.