Background: Propofol is a commonly used intravenous induction agent but it is associated with intense pain on injection in majority of patients.Various methods have been studied to reduce the propofol induced pain. Lignocaine, a local anesthetic agent and Ondansetron, a 5HT3 receptor antagonist,both have been shown to effectively reduce the pain due to propofol injection. So aim of our study was to compare the efficacy of low dose lignocaine (0.1 mg/kg) and ondansetron (0.1 mg/kg) pretreatment to reduce the propofol induced pain on injection. Methods: The present study was conducted at our institute included one hundred adult patients of either sex, aged 18-60 years, with American Society of Anesthesiologists (ASA) grade 1 and 2 scheduled for various elective surgeries under general anesthesia. All the patients were randomly allocated into two groups of 50 patients each; Group L (Lignocaine group) received lignocaine (2%, preservative free) 0.1 mg/kg and Group O (Ondansetron group) received ondansetron 0.1 mg/kg (both diluted up to 5ml in normal saline) as pretreatment before induction of general anesthesia using propofol 1%, 2 mg/kg. A tourniquet was applied on the same upper arm with a pressure of around 70 mm Hg for venous occlusion to about 20 seconds. After giving the pretreatment drug, the tourniquet was released, propofol was administered thereafter and the patients were assessed for level of pain intensity using the scale advocated by McCririck and Hunter. Results: The incidence of propofol induced pain in Group L and Group O were 46% and 40% respectively.(P>0.05) In Group L, out of 23 patients, 6 patients recalled pain whereas in Group O, 13 patients recalled pain out of 20 patients, but both incidence and recall of pain were found to be statistically insignificant between two groups. (P>0.05) 24% patients in Group L and 16% patients in Group O had experienced post operative nausea and vomiting (PONV) which was also statistically insignificant (P>0.05). The various hemodynamic parameters remained stable. Conclusion: Although we had used lignocaine at its lower dose (0.1 mg/kg) as pretreatment but both lignocaine and ondansetron were found to be equally effective in reducing propofol induced pain on injection.