Background: It's common knowledge that getting propofol via an IV may be a painful experience. The most effective remedy for reducing propofol-induced pain is unclear, despite the widespread use of a number of physical and pharmaceutical techniques. We set out to evaluate how well lidocaine, granisetron, and hyoscine work as pretreatments for painful propofol injections. Methods: This double-blind, randomized controlled trial was conducted after receiving the approval of our institutional research ethics board. A total of 150 patients were included after providing informed consent, and participants were placed into three equal groups: group A received lidocaine pretreatment prior to the injection of propofol, group B received granisetron pretreatment prior to propofol injection and group C received hyoscine pretreatment prior to the injection of propofol. After propofol injection, all participants were asked to evaluate pain at 0, 5, 10, 15 and 20 seconds of injection. Results: There was no significant differences regarding the age, sex and ASA status. The most effective drug in reducing pain induced by propofol was lidocaine followed by hyoscine then granisetron. At 0 sec with induction of anesthesia 94% of patients had no pain Vs 86% in each hyoscine and granisetron group. After 20 sec of induction still lidocaine is the best drug in which 88% of patients had no pain Vs 70% for hyoscine and 60% for granisetron. Conclusions: Lidocaine was better than hyoscine and that hyoscine is better than gransteron in reducing the incidence of propofol injection pain with no effect on the hemodynamics of the patients and no major post-operative complications or adverse effects.