Topical anesthesia is widely advocated in pediatric dentistry practice to reduce pain and anxiety produced by administration of local anesthesia. Cryoanesthesia to lessen the injection pain has also been reported to be promising. However, sparse literature reports exist regarding clinical efficacy of these agents. Aim: The purpose of this study was to compare the efficacy of the refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluoroethane), benzocaine and ice on the pain perception during intraoral injection using visual analog scale (VAS) and sound, eye, motor (SEM) scale. Study design: In this Spit-mouth design study, a total of 160 patients between the age group of 5 and 8 years were selected and were randomly divided into two equal groups having 80 patients in each group. Results: Ice cone has shown lower mean scores (p < 0.001) as compared to benzocaine and refrigerant whereas no significant difference was observed between refrigerant and benzocaine (p > 0.05) on both the scales. Conclusion: Ice cone had shown significantly higher efficacy as compared to benzocaine and refrigerant. How to cite this article: Lathwal G, Pandit IK, Gugnani N, Gupta M. Efficacy of Different Precooling Agents and Topical Anesthetics on the Pain Perception during Intraoral Injection: A Comparative Clinical Study. Int J Clin Pediatr Dent 2015;8(2):119-122.