Background and Objectives: Propofol is the most frequently used intravenous anesthetic today. One of its side effects is the pain on injection. Various methods such as adding lidocaine, cooling or warming and dilution of the propofol solution have been used for reducing the pain. However, each of these methods comes with a degree of failure. We designed this double-blinded randomized clinical trial to evaluate the effects of ephedrine of the injection pain caused by propofol. Materials and Methods: Fifty patients, between 20-60 years old and in the ASA physical status I and II, were enrolled in this experimental study and randomly divided into two equal groups. The basal vital signs for all patients were recorded, and 30 seconds prior to the induction of anesthesia, either 70µg/kg of ephedrine (study group) or an equal volume of normal saline (control group) was administered without premedication. Then, 20% of propofol was administered to each patient, and the pain intensity was measured and recorded by both the Verbal Rating Scale (VRS grading 0-3) and Face Pain Scale (FPS grading 1-6). The remaining dose of propofol and atracurium were administered. Results: Patients of two groups were similar with respect to age, sex, ASA status, and basal vital signs (P>0.05). The mean degrees of pain severity, in the study and control group were 0.48 ± 0.51 and 1.08 ± 759 by VRS (P = 0.002), and 1.48 ± 0.586 and 2.04 ± 0.841 by FPS (P=0.009), respectively. Conclusion: Based on the results of the present study, also supported by other studies, it seems that administration of ephedrine prior to propofol is a suitable method for reduction of pain from propofol injection.