Objective:We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment.Methods:Eighty patients were enrolled. Patients in group S received ondansetron 4 mg in saline in the right hand followed 30 min later by 5 mL saline in the left hand along with venous occlusion. Group L patients received 4 mL of saline in the right hand followed by 5 mL 4 mg ondansetron in the left hand after 30 min. Two minutes later the occlusion was released. Patients received one-fourth of the calculated total dose of propofol, and their level of pain was graded on a scale of 0 to 3, with 0 denoting no discomfort. Mean blood pressure and heart rates were also recorded. Continuous variables were checked for normality using Shapiro-Wilks test. Normal continuous variables were expressed as mean standard deviation and non-normal continuous variables were expressed as median interquartile range. T-test for the difference in the mean and paired test were used for normally distributed continuous variable whereas Mann-Whitney U test-Wilcoxon test and sign test were used for non-normally distributed variables. Repeated measure analysis of variance was used for a variable measured over different periods of time to control for the baseline effect on subsequent measures.Results:Our results demonstrated that both systemic administration 30 min before and local venous pretreatment with ondansetron were equally beneficial in reducing pain during propofol injection.Conclusion:A systemic administration of ondansetron may play a role in the attenuation of propofol injection pain.