Background: Pain on injection is a common adverse effect with propofol used for general anesthesia. Objectives: The alms of this study were to evaluate the analgesic effect of dexamethasone during propofol injection and investigate whether a combination of dexamethasone and lidocaine produced additional analgesic efficacy compared with either treatment alone. Methods: In a double-blind, prospective trial, patients scheduled to undergo elective plastic surgery were randomized to receive lidocaine 20 mg, dexamethasone 6 mg, combination lidocaine 20 mg and dexamethasone 6 mg, or normal saline with venous occlusion for 1 minute, followed by administration of 25% of the total calculated dose of propofol (2.5 mg/kg) into a dorsal hand vein. Pain intensity and incidence were evaluated during a 10-second pause before the induction of anesthesia, using a 4-point verbal rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe); a score of 1 to 3 was counted as pain. Patients were monitored hourly for 24 hours postsurgery by a blinded investigator for adverse effects at the injection site (eg, pain, edema, wheal, flare response). Results: A total of 140 (35 per group) Korean patients (91 women, 49 men; mean [SD] age, 47 [14] years; mean [SD] height, 162 [8] cm; and mean [SD] body weight, 60 [8] kg) completed the study. Demographic variables were similar among groups. With respect to pain intensity, mean pain score was significantly less in the combination group than in the lidocaine or dexamethasone groups (P < 0.01, respectively), although the median pain scores for all groups were 0. The incidence of pain associated with propofol injection was reduced significantly in the combination group compared with the lidocaine or dexamethasone group (0% vs 34.3% and 37.1%, respectively; both, P < 0.01). One patient (in the combination group) complained of perineal itching immediately following injection; however, this subsided within a few seconds and did not require any intervention. No other adverse effects at the injection site were observed in any patient in the 24 hours postsurgery. Conclusion: Combination lidocaine 20 mg and dexamethasone 6 mg, with venous occlusion for 1 minute, was more effective than lidocaine 20 mg or dexamethasone 6 mg alone for pain control during propofol injection in these Korean patients.