Abstract : Propofol is an intravenous induction agent with high incidence of pain on injection. The aim of this randomized, triple blinded, placebo-controlled study was to assess efficacy of pre-treatment with various drugs to alleviate the propofol injection pain. 344, American Society of Anesthesiologists (ASA) I and II adult patients scheduled for elective surgical procedures under general anesthesia (GA) were included in the study. They were randomly divided into four groups with each group having 86 patients. Group L received pre-treatment with intravenous (I.V) lignocaine 0.5mg/Kg, group D received dexmedetomidine 0.25µg/Kg I.V, group NT received I. V. nitroglycerine 0.1µg/Kg and group NS was control group. Venous occlusion was applied to forearm using a pneumatic tourniquet and was inflated to 70 mm of Hg for 1 minute. Study drug was injected, tourniquet was released and then 25% of the calculated dose of propofol was given I. V. over 10 sec. Patients were assessed for pain at injection site at 0 sec, 30 sec and 60 seconds after injection of propofol using McCrirrick and Hunter Pain scale. Unpaired student’s t-test and chi-square test/Fisher’s exact test were used to analyze results. The order of efficacy of the study drugs in attenuation of pain on propofol injection was lignocaine> dexmedetomidine> nitroglycerine > control. Pre-treatment with 0.25µg/Kg of dexmedetomidine is effective as lignocaine in preventing propofol injection pain.