BACKGROUND Despite various strategies designed for preventing pain from propofol injection, it is still common and distressing to the patients. The purpose of the present study was to investigate the adequate effect-site concentration (Ce) of remifentanil to prevent pain due to propofol injection. METHODS A total of 160 adults scheduled for elective surgery were randomly assigned to one of four groups receiving normal saline (group S) or remifentanil at a Ce of 2 (group R2), 3 (group R3), or 4 ng/ml (group R4), administered via target-controlled infusion, followed by the injection of 2 mg/kg of propofol (delivered with 1% lipid propofol). The severity and incidence of injection pain were assessed on a four-point scale. RESULTS The incidence of propofol injection pain was significantly lower in group R2, R3, or R4 than in group S (30%, 5%, or 2.5% vs. 70%, respectively). Moreover, the intensity of the pain was lesser in group R2, R3, or R4 than in group S. However, the incidence or severity of injection was not different between groups R3 and R4. CONCLUSIONS During the induction of balanced anesthesia using propofol injection, pretreatment with remifentanil at a target Ce of 3 ng/ml effectively reduced propofol injection pain in adults.