AbstractBackground and Objectives: Intravenous Cannulation is a pain full procedure. Pain associated with intravenous cannulation can be decreased by using local anaesthetics. This study was conducted to evaluate the efficacy of EMLA cream against the reduction of the venipuncture pain during IV cannulationin comparison with Ethyl chloride spray. Methods: This single center, prospective randomized study with two parallel groups was conducted at Department of Anaesthesiology, Critical Care and Pain Management, S.S Institute of Medical Sciences, Davanagere. A total of 100 subjects admitted due to various illnesses were enrolled into the study. Study subjects were randomly divided into two groups viz. G1 and G2 with 50 subjects in each group. Subjects in G1 were anesthetized with topical application of EMLA cream, and in G2 with Ethyl Chloride spray. Results: The results of VAS score depicted that following application of EMLA cream causes mild venepuncture pain during intravenous cannulation, whereas Ethyl chloride spray causes moderate venepuncture pain during intravenous cannulation. Furthermore, our study findings delineated that EMLA cream was safe to use without any side effects when compared to Ethyl chloride spray wherein burning sensation, itching and redness like side effects were experienced by study subjects. Conclusion: EMLA cream is safe and effective in reduction of venipuncture pain during IV cannulation.