AbstractContext: Propofol is a sedative-hypnotic intravenous anaesthetic agent. It causes a high incidence of pain during intravenous injection which leads to patient dissatisfaction. Aim: The aim of this study was to determine whether pre-treatment with intravenous lignocaine, ondensetron and fentanyl was effective in reducing propofol induced pain. Settings and Design: In a prospective, randomized, double blind study 150 ASA physical status I and II patients, aged 20-60 years, undergoing elective surgery under general anesthesia, were allocated randomly into three groups. Methods and Material: Group A received IV lignocaine 42 mg (2 ml), Group B received IV ondansetron 4mg and Group C received IV fentanyl 100 mcg. Mid-arm was occluded before drug injection then released after 1 min followed by propofol injection. Patients were assessed according to Mc Crirrick and Hunter pain scoring system at 0, 5, 10, 15 and 20 seconds. Statistical analysis: ANOVA with Dunnett’s post hoc test and chi-square test were used to analyze results. Results: Two patients in Group A and one patient in Group B had ‘no pain’ during the observation period. Group B and Group C have more ‘mild pain’ than Group A while it is comparable in Group B and C. ‘Moderate pain’ is comparable between Group A and B while Group A has more ‘moderate pain’ than Group C and Group B has more ‘moderate pain’ than Group C. Only one patient in Group A had ‘severe pain’. Conclusion: Pre-treatment with lignocaine, ondensetron and fentanyl was effective in reducing pain on propofol injection but the superiority of one drug over the other cannot be commented.