Background: General anesthesia is preferred during surgeries to reduce the pain stimuli in patients and to increase the precision of surgical procedure. Propofol is amongst the most widely used general anesthetic agent with limitation of induced pain during administration. Current study was conducted to compare the effect of intravenous pre-administration of various drugs in attenuating propofol induced pain. Methods: A comparative observational study was conducted on patients of either sex and aged between 18-60 years. Patients were divided in three groups, who received intravenous lignocaine, dexamethasone and combination of lignocaine-dexamethasone respectively to attenuate propofol induced pain. Different variables like HR, SBP, DBP, MAP, RR SpO2 and any adverse events were monitored in all the patients. Results: The 46.66% and 53.33% patients who received lignocaine and dexamethasone alone perceived propofol induced mild to moderate pain; while only 23.33% patients who received lignocaine and dexamethasone in combination perceived mild propofol induced pain. The propofol induced pain event was persistent in only 2 out of 30 patients after a time lapse of 30 seconds for the group receiving lignocaine and dexamethasone in combination. Whereas, the pain event was present even after time lapse of 30 seconds in 08 and 07 out of 30 patients of groups receiving lignocaine and dexamethasone alone.Conclusions: Pre-administration of lignocaine and dexamethasone in combination attenuated the propofol induced pain more significantly in comparison to single administration of mentioned drugs. No significant adverse events except perianal irritation were observed in some patients who received combination of lignocaine and dexamethasone intravenously.