Background: Paediatric patients are a population with a high level of anxiety. The pre-vention of perioperative stress in a frightened child is important to render the child calm and cooperative for smoother induction. Intranasal premedication is easy and safe, and the drug is rapidly absorbed into the systemic circulation, ensuring early onset of seda-tion in children and good effectiveness.Methods: 150 patients in the age group 2-4 years, ASA class I, undergoing elec-tive surgical procedures were enrolled. The patients were randomly divided into 3 groups: a DM group (receiving intranasal dexmedetomidine 1 & mu;g kg-1 and midazolam 0.12 mg kg-1), a DK group (receiving intranasal dexmedetomidine 1 & mu;g kg-1 and keta-mine 2 mg kg-1), and an MK group (receiving intranasal midazolam 0.12 mg kg-1 and ketamine 2 mg kg-1). After 30 minutes of administration of the drugs, the patients were assessed for parent separation anxiety, sedation, ease of IV cannulation, and mask acceptance.Results: The comparison among the 3 groups showed a statistically significant dif-ference for ease of IV cannulation and mask acceptance at 30 minutes, with a P-value of 0.010 with CI of 0.0-0.02, and P-value 0.007 with CI 0.0-0.02, respectively. The parent separation anxiety and sedation score at 30 minutes was statistically insignificant with a P-value of 0.82 with CI of 0.03-0.14 and P-value 0.631 with CI of 0.38-0.58, respectively.Conclusions:The combination of midazolam and ketamine had a better clinical profile for premedication as compared to other combination drugs used in our study in terms of IV cannulation and acceptance of masks with a comparable decrease in separation anxiety from parents and adequate sedation.