Propofol causes pain on IV injection in 28%-90% of patients. A number of techniques have been tried to minimize propofol-induced pain, with variable results. We compared the efficacy of pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg and lidocaine 40 mg after venous occlusion for prevention of propofol-induced pain. One-hundred-twenty-four adult patients, ASA physical status I-II, undergoing elective surgery were randomly assigned into 4 groups of 31 each. Group I received normal saline, group II received lidocaine 2% (40 mg), and groups III and IV received thiopental 0.25 mg/kg and 0.5 mg/kg, respectively. All pretreatment drugs were made in 2 mL and were accompanied by manual venous occlusion for 1 min. Propofol was administered after release of venous occlusion. Pain was assessed with a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain at the time of propofol injection. Twenty-four patients (77%) complained of pain in the group pretreated with normal saline as compared with 12 (39%), 10 (32%), and 1 (3%) in the groups pretreated with lidocaine 40 mg, thiopental 0.25 mg/kg, and thiopental 0.5 mg/kg, respectively (P < 0.05). Thiopental 0.5 mg/kg was the most effective treatment. We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with venous occlusion for 1 min for prevention of pain associated with propofol injection. CONCLUSIONS Pain associated with IV injection of propofol is seen in 28%-90% patients. Pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg after manual venous occlusion for 1 min effectively attenuated pain associated with propofol injection. Thiopental 0.5 mg/kg was the most effective in prevention of propofol pain and can be used routinely.