Midazolam/ketamine sedation has been used successfully in children undergoing painful invasive procedures. The authors prospectively assessed inter- and intra-individual variability in ketamine dosage for sedation in repetitive invasive procedures in children with malignancies. A total of 92 invasive procedures (58 lumbar punctures, 34 bone marrow biopsies; range: 2-9 procedures/patient) were performed on 25 children (median age: 12 years). Intravenous sedation consisted of 0.1 mg midazolam/kg and 0.5-1.0 mg ketamine/kg. Incremental dosages of ketamine (0.33 mg/kg) were given if necessary to achieve or maintain deep sedation. Primary outcome measure was the inter- and intraindividual ketamine dosage required to achieve adequate sedation; secondary outcome measures were the number of procedures with adequate sedation (Ramsay score of > 4), the number of adverse side effects, and the need for therapeutic interventions. All 92 invasive procedures were completed with satisfactory sedation levels in 88 procedures (95.7%). There was a great inter- and intraindividual variability in ketamine dosage required to achieve or maintain adequate sedation. In 12% of procedures side effects were seen, which required no or only minor interventions. Due to great inter- and intraindividual differences, ketamine dosage should be titrated toward the desired level of sedation. Thus, ketamine can be adjusted to the individual's need while achieving adequate sedation.