Introduction: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The American Pain Society (APS) has officially declared pain as the fifth vital signs. Intramuscular (IM) injection is a common procedure that nurses frequently carry out and observe pain and distress to the recipient. The aim of the study was to compare the effectiveness of ice cube and vapocoolant spray as an anesthetic pre-treatment for IM injection among patients in selected hospital, East Sikkim. Method: A quantitative factorial design study was conducted on patients, receiving intramuscular tetanus toxoid injection at Central Referral Hospital, Gangtok, East Sikkim. Total 50 participants were selected using simple random sampling technique. The demographic data of the patients were collected using structured questionnaire and a Standardized Numerical Pain Rating Scale was used to assess the pain level after the administration of intramuscular tetanus toxoid injection using ice cube and vapocoolant spray as an anesthetic treatment. Result: The study findings highlights that the mean and SD for intensity of pain in ice cube group was 1.84±1.313 and in vapocoolant group was 2.92±1.470 with mean difference was 0.157 and (t=2.740 and p=0.009) and p<0.05 level of significance which was statistically significant and indicates that ice cube was more effective than vapocoolant in reducing the intensity of pain among patients as an anesthetic pre-treatment for IM injection. The findings also revealed that there is no association between the level of pain with selected demographic variables. Conclusion: The study found that ice cube was more effective than vapocoolant spray to reduce the level of pain while administering IM injection. The study intervention would help the health care professionals mainly the staff nurses to execute the practice of using ice cube before IM injection to reduce pain.