BACKGROUND: The injection pain of microemulsion propofol is frequent and difficult to prevent. This study examined the prevention of pain during microemulsion propofol injection by pretreatment with different doses of remifentanil or saline, and premixing of lidocaine. METHODS: One hundred sixty ASA physical status 1-2 adult patients scheduled for elective surgery were enrolled into one of four groups (n = 40, in each). The patients received saline (group LS), remifentanil 0.3 microg/kg (group LR 0.3), remifentanil 0.5 microg/kg (group LR 0.5), or remifentanil 1.0 microg/kg (group LR 1.0), and after 90 seconds received an injection of 2 mg/kg microemulsion propofol premixed with lidocaine 40 mg. Pain was assessed on a four-point scale during microemulsion propofol injection. RESULTS: The incidence of microemulsion propofol-induced pain was significantly lower in the LR 0.3, LR 0.5 and LR 1.0 groups than in the LS group (37.5%, 12.5% and 10% vs 65%, respectively). The LR 0.5 and LR 1.0 groups showed significantly less frequent and intense pain than the LR 0.3 group. However, both incidence and severity of pain were not different between LR 0.5 and LR 1.0 groups. CONCLUSIONS: The combination of remifentanil and lidocaine is effective in alleviating pain associated with a microemulsion propofol injection compared with just lidocaine. Remifentanil 0.5 microg/kg had a similar analgesic effect compared to the 1.0 microg/kg dose.