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This randomized, double-blind, placebo-controlled study was carried out to determine the effect of esmolol on the incidence and severity of pain during propofol injection using a venous retention technique, and to compare it with lidocaine and placebo.After institutional ethical approval, 150 ASA I-II patients (ages 21–70) undergoing general anaesthesia for elective surgery were randomized to receive esmolol (0.5 mg/kg) (n = 50), lidocaine (0.5 mg/kg) (n = 50) or saline (placebo group, n = 50) diluted into a 5 ml solution after tourniquet application (70 mmHg) on the forearm. The occlusion was released after 30 seconds and 25% of the calculated induction dose of propofol was administrated at the rate of 0.5 ml/s. The patients were observed and asked immediately if they had pain in the arm, and the response was recorded.Twenty-seven patients in the esmolol group, 28 in the lidocaine group, and 8 in the placebo group reported no pain (both groups vs. placebo, p < 0.001). Mild pain was experienced in 21 patients in the esmolol group, 19 in the lidocaine group and six in the placebo group. Moderate pain was observed in two patients in the esmolol group, three in the lidocaine, and 11 in the placebo group (both groups vs. placebo, p < 0.05). No patient in the esmolol and lidocaine groups had severe pain, compared to 25 in the placebo group.We conclude that, using a retention technique, esmolol reduces the pain of propofol injection as effectively as lidocaine, without causing any significant adverse effects.