Different pharmacologic agents have been used for sedation in children undergoing invasive procedures. The authors prospectively compared the efficacy, the occurrence of adverse effects, cardiovascular parameters, oxygen saturation and induction, and recovery time in propofol with or without morphine versus midazolam/ketamine sedation for procedural sedation in children with malignancies and hematologic disorders. Fifty children received either propofol with or without morphine or ketamine/midazolam sedation for invasive procedures. Intravenous sedation consisted of 0.1 mg midazolam/kg and 1.0 mg ketamine/kg or 2 mg propofol/kg with or without 0.1 mg morphine/kg. Incremental dosages of ketamine or propofol were given, if necessary, to achieve or to maintain adequate sedation levels. Systolic and diastolic blood pressure, heart rate, oxygen saturation, time to induce sedation, recovery time, and adverse effects were recorded. All invasive procedures were successfully completed, with satisfactory sedation levels in all 25 patients in the propofol group and 23 of the 25 patients in the ketamine group. In 14 of the 25 procedures in the propofol group and 4 of the 25 procedures in the ketamine group, sedation was associated with side effects, the most common being oxygen desaturation. There was a significant increase in diastolic blood pressure after ketamine medication and a significant decrease in systolic and diastolic blood pressure and heart rate in the propofol group. Induction and recovery times in the propofol group were significantly shorter. Both regimens for procedural sedation are efficacious in achieving satisfactory sedation levels for invasive procedures. Propofol offers a quicker onset of sedation and a faster, smoother recovery but is associated with a higher rate of side effects. Considering the substantial rate of adverse effects, these procedural sedations should be performed only by physicians trained in advanced airway management and life support.