BACKGROUND: Although ondansetron is effective at preventing and treating postoperative nausea and vomiting (PONV), the optimal timing of its administration has not been established. In this study we evaluated the effect of the timing of ondansetron administration on its antiemetic efficacy in patients undergoing thyroidectomy. METHODS: One hundred and twelve patients undergoing thyroidectomy were randomized to receive placebo (control group, n = 40) or 70microgram/kg of ondansetron prior to induction (Pre-group, n = 36), or 70microgram/kg of ondansetron at the end of surgery (Post- group, n = 36). The incidence of PONV, adverse events, the need for rescue antiemetics, and nausea severity scores were assessed at 0 to 1 hour and 1 to 24 hours postoperatively. RESULTS: During the first 24 hours after anesthesia, the incidences of PONV in the control, and Pre- and Post-groups were 62.5%, 52.8%, and 52.8%, and there was no significant difference among the groups. During the period 1 hour to 24 hours after anesthesia, the incidences of vomiting (with nausea) and rescue antiemetics were significantly lower in the Pre- and Post-groups than in the control group (P < 0.05). Overall, the incidence of vomiting (with nausea) was significantly lower in the Pre-group than in the control group and the incidence of rescue antiemetics was significantly lower in the Pre- and Post-groups than in the control group (P < 0.05). CONCLUSIONS: In patients with thyroidectomy, the perioperative administration of 70microgram/kg ondansetron was found to reduce the incidence of vomiting and the need for rescue antiemetics. However, the timing of ondansetron administration did not affect antiemetic efficacy.