Pediatric patients undergoing cardiac catheterization usually need deep sedation. In this study, 60 children were randomly allocated to receive sedation with either a ketamine–propofol combination (KP group, n = 30) or a ketamine–propofol–dexmedetomidine combination (KPD group, n = 30). Both groups received 1 mg/kg of ketamine and 1 mg/kg of propofol for induction of sedation, and the KPD group received an additional 1 μg/kg of dexmedetomidine infusion during 5 min for induction of sedation and a maintenance infusion of 0.5 μg/kg/h. In both groups, 0.2 mg/kg of propofol was administered as a bolus to maintain a Ramsey sedation score (RSS) greater than 4 throughout the procedure. None of the patients in either group required intubation. In the KP group, one patient required mask ventilation. The chin-lift maneuver needed to be performed for eight patients in the KP group and one patient in the KPD group (p < 0.05). Adding dexmedetomidine to the ketamine–propofol combination decreased movement during the procedures. The heart rate in the KPD group was significantly lower after induction of sedation and throughout the procedure (p < 0.05). No significant differences in systolic blood pressure, diastolic blood pressure, or respiration rates were found between the two groups (p > 0.05). The mean recovery time was longer in the KP group (5.86 vs 3.13 min; p < 0.05). Adding dexmedetomidine to a ketamine–propofol combination led to a reduced need for airway intervention and to decreased movement during local anesthetic infiltration and throughout the procedure. The recovery time was shorter and hemodynamic stability good in the KPD group.