Background and aims: Pain on injection of propofol is a well-known side effect faced by all anesthesiologists in their day to day practice. The aim of the study was to assess the efficacy of low dose ketamine in the prevention of pain on injection of propofol. Materials and methods: A prospective, randomized, and double-blind study was conducted on 100 patients, from either gender, aged 20-50 years, of the American Society of Anaesthesiologists Grade I or II, scheduled for various surgeries under general anesthesia. The patients were randomly divided into two groups of 50 each to receive either ketamine 0.5 mg/kg (Group K) or saline (Group S) infusion over 10 min. Venous drainage was occluded manually for one minute. This was followed by an injection of propofol 2 mg/kg IV over 25s. The patients were asked for pain on injection every 5s until the loss of consciousness. The pain scoring was done using McCririck and Hunter scale. The primary outcome of the study was the incidence of pain on propofol injection. Secondary outcomes such as increased secretions, emergence agitation were recorded. Results: Nine patients in group K (18%) and 42 patients in group S (84%) developed pain on injection of propofol. The incidence of pain was statistically significant between the two groups (p = < 0.001). Three patients in group K (6%) and 23 (46%) patients in group S had severe pain (p = < 0.001). Three patients in group K experienced increased secretions, which was not significant in comparison with the other group (6% vs 0%, p = 0.242). Four patients in group K had emergence agitation, but this was again not statistically significant when compared to group S (8% vs 0%, p = 0.117). Conclusion: We conclude that pretreatment of a smaller dose of ketamine was effective in the prevention of pain on injection of propofol without major side effects.