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The incidence of pain associated with the injection of propofol still remains a problem. This study sought to examine the analgesic effects of inhaled nitrous oxide in oxygen on the prevention of propofol injection pain.Nitrous oxide in oxygen was compared with a lidocaine (20 mg)-propofol mixture and with propofol alone (control) in a prospective, randomized, observer-blinded study. ASA I and II patients (n = 135) scheduled for elective surgical procedures were studied. A standard propofol injection technique and scoring system to measure the pain on injection was used.Demographic variables were similar between the study groups. Without analgesia (control) 26 of 45 patients (58%) reported pain on injection compared with 11 of 45 patients (24%) in both the nitrous oxide (95% CI: 14-52%, P = 0.001) and lidocaine groups (95% CI: 14-52%, P = 0.001).The inhalation of a nitrous oxide/oxygen mixture significantly reduces the incidence of pain during propofol injection. This therapeutic stratagem was as effective as a lidocaine-propofol mixture.