BACKGROUND Propofol injection pain is a frequent and a well-known complaint distressing for the patients. Although the ethiology of this pain remains obscure, the ideal method for the prevention of propofol injection pain is still controversial. Local anesthetics, opioids, nonsteroidal anti-inflammatory drugs, ketamine, metoclopramide, droperidol have been tested. We aimed to conduct a study comparing various drugs with saline, lidocaine and together at the same time. METHODS In this randomized, double-blind, prospective trial a total of 250 patients (ASA I-II) undergoing elective surgery with general anesthesia were randomly allocated into five groups. After premedication of 3 mg midazolam im, patients received either 2 mL (0.02 mg) of remifentanil (n = 50, Group R), 2mL (40 mg) of lidocaine (n = 50, Group L), 2 mL (10 mg) of metoclopramide (n = 50, Group M), or 2mL (100 microg/kg) of ketamine (n = 50, Group K) and 2 mL of saline. Pain intensity was evaluated through the use of a verbal rating scale, 0 = none, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. RESULTS Pretreatment with remifentanil 0.02 mg, % 2 lidocaine 40 mg, metoclopramide 10 mg, and ketamine 100 microg/kg yields propofol induced pain 38%, 76%, 76%, and 58% respectively. Pretreatment with lidocaine or metoclopramide equally and significantly reduced the incidence and severity of propofol induced pain (76%). CONCLUSIONS Lidocaine and metoclopramide were equally and the most effective treatments in attenuating pain during intravenous injection of propofol compared to pretreatment with remifentanil and ketamine.