Background We sought to determine (1) whether the addition of prophylactic oral mosapride to a protocol including dexamethasone and ondansetron further reduces postoperative nausea and vomiting (PONV) compared with ondansetron alone or the combination of both; (2) whether preemptive application of oral mosapride provides additional clinical benefits for bowel function and appetite, thus improving functional recovery. Methods We randomized 240 patients undergoing total hip and knee arthroplasty

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... o receive placebo (Control, n = 80), dexamethasone (10 mg) before anesthesia induction (Dexa, n = 82), or dexamethasone (10 mg) before anesthesia induction as well as oral mosapride (5 mg) before and after surgery (Mosa+Dexa, n = 78). Patients were assessed at 0–6, 6–12, 12–24, and 24–48 h postoperatively. Primary outcomes were incidence and severity of PONV as well as complete response. Secondary outcomes were appetite, time until first defecation and ambulation, patient satisfaction score, and length of hospital stay. Results Mosa+Dexa patients showed significantly lower incidence of nausea at 6–12 h (3.8%) and over the entire evaluation period (6.4%), as well as a higher rate of complete response (89.7%) than other patients. Mosa+Dexa patients required less time to achieve first defecation and ambulation, they were hospitalized for shorter time, and they were more satisfied with clinical care. Conclusion Addition of oral mosapride further reduced incidence of PONV, especially postoperative nausea, during 6–12 h postoperatively. Moreover, preemptive application of oral mosapride can further improve appetite, bowel function, ambulation and length of hospital stay. Trial registration The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896), prospectively registered on 27/04/2018.