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Background:The authors hypothesized that the continuous infusion of ramosetron 0.15 mg following a 0.15 mg bolus administration would maintain higher 5-hydroxytryptamine type 3 receptor occupancy levels and be more effective in preventing postoperative nausea and vomiting (PONV) than a 0.3 mg single bolus administration. We conducted a study to compare the efficacy of single bolus ramosetron administration with the combination of continuous infusion following intravenous bolus administration for PONV prophylaxis. Methods: One hundred and fifty female patients undergoing thyroidectomy were allocated randomly to one of three groups to receive a placebo (Group 1, n = 49), 0.3 mg of IV ramosetron (Group 2, n = 53), or the continuous infusion of 0.15 mg ramosetron following a bolus administration of 0.15 mg of ramosetron (Group 3, n = 48). Anesthesia was maintained with sevoflurane and N2O. The incidence of PONV, nausea severity, and use of rescue antiemetics during the postoperative 24 hours were recorded. Results: Group 1 showed higher incidences of PONV during the postoperative 24 hour than Group 2 (81% vs. 58%, P = 0.02) and Group 3 (81% vs. 48%, P < 0.01), but there was no difference between Groups 2 and 3 (P = 0.39). The use of rescue antiemetics was significantly lower in Groups 2 and 3 than Group 1 during the postoperative 6 to 24 hours. Conclusions: There were no significant differences of incidence and severity of PONV between ramosetron 0.3 mg single bolus administration and the combination of ramosetron infusion after 0.15 mg bolus administration. (Anesth Pain Med 2016; 11: 166-171)