Background & objective: Preoperative anxiety in pediatric patients is associated with poor cooperation, increased anesthetic requirements, and adverse postoperative outcomes. Oral premedication with midazolam is common, but its effectiveness may be suboptimal when used alone. This study aimed to evaluate the efficacy and safety of a combination of oral midazolam and ketamine compared to oral midazolam alone in children aged 1 to 6 years undergoing elective surgery. Methodology: A prospective, randomized, double-blind clinical trial was conducted involving 62 ASA I/II children scheduled for elective surgery under general anesthesia. Participants were randomized into two groups: Group M received oral midazolam 0.5 mg/kg, and Group MK received midazolam 0.25 mg/kg with ketamine 3 mg/kg, both diluted in paracetamol syrup. Sedation scores were recorded at 5-minute intervals up to 20 minutes post-administration. Behavioral responses were assessed at parental separation and during mask induction. Heart rate and oxygen saturation were monitored, and adverse events were noted. Statistical analysis was performed using SPSS v22.0, with P < 0.05 considered significant. Results: Group MK demonstrated significantly lower sedation scores at 5, 15, and 20 minutes (P = 0.004, 0.036, 0.001 respectively). Behavioral scores at parental separation and induction were also significantly better in Group MK (P < 0.001, P = 0.001). Mild but significant increases in heart rate were noted in Group MK at 5, 10, and 20 minutes (P < 0.05), with no respiratory compromise in either group. Adverse events were minimal, with three transient cases of nystagmus and two instances of drug rejection noted in the combination group. Conclusion: The combination of oral midazolam and ketamine provides earlier onset, deeper sedation, and improved behavioral responses compared to midazolam alone, with a comparable safety profile. This regimen offers a superior alternative for pediatric premedication in elective surgical settings. © 2025 Elsevier B.V., All rights reserved.