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Purpose-To assess the impact of a multimodal antiemetic protocol on postoperative nausea and vomiting (PONV) after LeFort I osteotomy.Methods-Consecutive subjects undergoing LeFort I osteotomy with or without additional procedures at a single academic institution were recruited as the intervention cohort for an IRBapproved prospective clinical trial with a retrospective comparison group. The intervention cohort was managed with a multimodal antiemetic protocol including total intravenous anesthesia; prophylactic ondansetron, steroids, scopolamine, and droperidol; gastric decompression at surgery end; opioid-sparing analgesia; avoidance of morphine and codeine; prokinetic erythromycin; and minimum 25 mL/kg fluids. The comparison group consisted of consecutive subjects from a larger study who underwent similar surgical procedures prior to protocol implementation. Data including Please address correspondence to: Dr. Jay Anderson, 101 Manning Dr CB 7450, Chapel Hill, NC 27599, janderson@aims.unc.edu, 919.537.3721 phone, 919.537.3407 fax. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-The intervention (n=93) and comparison (n=137) groups were similar in terms of gender (58% and 65% female, P=0.29), race (72% and 71% Caucasian, P=0.85), age (median 19 and 20 years old, P=0.75), proportion of subjects with known risk factors for PONV (P=0.34), percentage undergoing bimaxillary surgery (60% for both groups), and percentage for whom surgery time was over 180 minutes (63% versus 59%, P=0.51). NIH Public AccessPrevalence of PON was significantly lower in the intervention group than the comparison group (24% versus 70%, P<0.0001). Prevalence of POV was likewise significantly lower in the intervention group (11% versus 28%, P=0.0013). The likelihood that subjects in the comparison group would experience nausea was 8.9 and vomiting 3.7 times higher than in the intervention group.Conclusion-This multimodal protocol was associated with substantially decreased prevalence of PONV in subjects undergoing LeFort I osteotomy.