Intravenous administration of rocuronium bromide causes pain at the site of injection in most patients. The mechanism that leads to this side effect is still unknown and multiple drugs' pretreatments were used to prevent its occurrence with varying success rates. The study aimed to evaluate the effects of the pretreatment with lidocaine, fentanyl, and remifentanil using a venous occlusion technique in preventing pain caused by intravenous injection of rocuronium during induction of general anesthesia. Two hundred patients, ASA I-II, requiring various types of surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were pre-educated to report pain severity on rocuronium injection on a 4-point severity scale. Patients were allocated randomly using sealed envelopes method into one of four pretreatment groups: (Xylocaine group, 50), Remifentanyl group 50), (Fentanyl group, 50), and (Normal saline group, 50). After venous occlusion, study drugs were injected and the venous occlusion was maintained for one minute. Rocuronium was then administered and patients were asked to report their pain Compared to control group, all pretreatment drugs were effective in reducing pain on rocuronium injection. Xylocaine was the most effective (Mean difference-1.42, P <0.001), followed by Remifentanil (Mean difference-1.32, P <0.001) and Fentanyl (Mean difference-0.50, P <0.001) in reducing pain on rocuronium injection. Remifentanil was statistically comparable to Xylocaine (P = 0.820) and both drugs were superior to Fentanyl in reducing pain on rocuronium injection. Remifentanyl is a better choice of opioid in preventing pain on rocuronium injection using venous occlusion technique than fentanyl, with efficacy comparable to Xylocaine.