Aim: This study aims to compare the efficacy of magnesium sulfate, tramadol, ketorolac, and lignocaine in attenuating pain during intravenous propofol injection.Materials and Methods: This prospective, randomized, double-blind study was conducted on 120 adult patients aged 18–60 years, classified as ASA I or II, undergoing elective surgeries under general anesthesia. Patients were randomized into four groups (n=30 each): Group M received 50 mg of magnesium sulfate, Group T received 50 mg of tramadol, Group K received 30 mg of ketorolac, and Group L received 40 mg of lignocaine. The drugs were diluted to 5 mL with saline and administered before propofol injection. Pain during injection was assessed using a four-point verbal rating scale (VRS). Statistical analysis was performed using one-way ANOVA and chi-square tests, with p < 0.05 considered significant.Results: Demographic parameters were comparable across groups (p > 0.05). Lignocaine showed the most effective pain attenuation, with 83.33% of patients reporting no pain (VRS score 0), followed by magnesium sulfate (66.67%), tramadol (60.00%), and ketorolac (53.33%) (p < 0.01). Mean pain scores were lowest in Group L (0.20 ± 0.43) and highest in Group K (0.63 ± 0.70) (p < 0.05). Adverse events were minimal and comparable, with lignocaine showing the least incidence. Patient satisfaction was highest in Group L (86.67%) and lowest in Group K (60.00%) (p < 0.01).Conclusion: Lignocaine is the most effective agent for attenuating propofol injection pain, with magnesium sulfate serving as a viable alternative. Tramadol and ketorolac showed moderate efficacy but were less effective compared to lignocaine and magnesium sulfate. These findings reinforce the use of lignocaine as the gold standard for pain prevention during propofol injection.