Postoperative nausea and vomiting (PONV) remains a distressing and common problem after tonsillectomy with an incidence ranging from 40-73% in those who did not receive prophylactic antiemetic. This study was done to identify the minimum effective IV dose of ondansetron to decrease the incidence and severity of PONV in the dexamethasone (150ug/kg) pretreated children undergoing adenotonsillectomy. In this prospective, randomized, doubleblinded, placebo-controlled study, 150 children (3-12 years old) received dexamethasone 150g/kg IV (maximum 8mg) premedication were randomly assigned to receive either placebo (saline) or ondansetron in a dose of 25, 50, 75 or 150g/kg IV immediately after induction of anesthesia. All children received standardized perioperative care, including surgical and anesthetic techniques, IV fluid, postoperative analgesic and rescue antiemetic (RAE). The incidence and severity of PONV were recorded in a standardized fashion at the intervals 0-2, 2- 12 and 12-24h postoperatively. The time to first postoperative analgesic, total analgesic consumptions, the need for rescue antiemetic (RAE), the fast tracking time (FTT), the time to first oral intake and parent's satisfaction score were recorded as clinically true outcome measures. The five treatment groups were similar with respect to patients's characteristics and operative data. There was no significant difference with respect to the incidence (P>0.05) or severity (P>0.05) of PONV between the placebo and 25g/kg ondansetron group during the study period (0-24h). The incidence of early (0-2h), delayed (2-12h), and late (12-24) PONV were significantly less in the 50 (P<0.05), 75 (P<0.05) and 150 (P<0.05) g/kg ondansetron groups compared with placebo. The incidence of 24h PONV was 43, 37, 13, 10 and 7% in placebo, 25, 50, 75 and 150g/kg ondansetron groups, respectively. The PONV severity scores (0-3) were significantly less (p<0.05) in children who received ondansetron in a dose of 50g/kg or more compared with the placebo. There was no statistically significant difference with respect to the incidence (P>0.05) or the severity (P>0.05) of PONV between the 50, 75 and 150g/kg ondansetron groups. The time to first postoperative analgesic, the total postoperative analgesic consumptions, the need for RAE, the time to first oral intake and the fast tracking time (FTT) were significantly less (P<0.05) in children who received 50, 75 and 150 g/kg ondansetron in comparison with placebo. The parent's satisfaction scores were significantly high (P<0.05) for those children who received ondansetron in a doses of 50g/kg or more compared with placebo. There was no significant difference with respect to the clinically true outcome measures in children who received ondansetron in dose of 50g/kg or more. In conclusion, ondansetron 50g/kg IV was the minimum effective IV dose to decrease the incidence and severity of PONV in dexamethasone (150g/kg IV) pretreated children undergoing adenotonsillectomy. This dose was associated with a significant reduction in the time to first postoperative analgesic, total analgesic consumptions, the need for rescue antiemetic (RAE), the time to first oral intake, the fast tracking time (FTT) and a high parent's satisfaction scores. Increasing the dose of ondansetron to 150g/kg provided no significant benefits in reducing the incidence or severity of PONV in dexamethasone (150g/kg IV) pretreated children undergoing adenotonsillectomy