Background: Chemotherapy-induced nausea and vomiting remains a significant problem for children with leukemia. There is limited evidence to support using prophylactic antiemetic prior to the administration of intrathecal chemotherapy.Objective: Determine whether vomiting and nausea associated with intravenous ketamine and intrathecal chemotherapy may be reduced by the addition of prophylactic dexamethasone in children.Method:A randomized, double-blinded, crossover, placebo-controlled trial was completed in 33 children receiving intrathecal chemotherapy with methotrexate and ketamine sedation at Pharmongkutklao Hospital. Patients were randomly assigned in a double-blinded fashion to receive one of two interventions during the first period, either an infusion of normal saline or intravenous dexamethasone at 0.25 mg/kg/dose. Each patient acted as his or her own control, and each patient was studied at two time-points.Results: Period effect, sequence effect, and carry over effect were not demonstrated. The absolute risk reduction of vomiting was significantly greater after infusion of dexamethasone than after placebo at 33.3 % (p=0.02). The number needed to treat was three to prevent one episode of vomiting. Fifteen patients in the treatment group reported nausea versus 26 patients in the placebo group (p= 0.007). In the group of patients treated with dexamethasone, five required antiemetic vs. 16 of those receiving placebo (p=0.02). There was no complication from dexamethasone.Conclusion: Intravenous dexamethasone reduced vomiting associated with intrathecal chemotherapy and ketamine sedation, without significant side-effects. It may be recommended a reasonable option before intrathecal chemotherapy.