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Objectives The aim of the study was to evaluate the antiemetic effects of maropitant, after oral administration, in cats receiving morphine and dexmedetomidine. Methods This prospective, blinded, randomized controlled trial involved 98 healthy female domestic shorthair cats. Cats were randomly assigned to receive maropitant PO 8 mg total (group M) administered 18 h prior to sedation with intramuscular dexmedetomidine 20 µg/kg and morphine 0.1 mg/kg, or no antiemetic treatment (group C). The occurrence of signs of nausea (sialorrhea and lip-licking), retching and emesis during the 30 mins following administration of dexmedetomidine and morphine was measured for each group. Results Two cats were excluded from the investigation. Cats in group M (n = 46) received an average of 2.5 mg/kg of maropitant PO. Compared with group C (n = 50), cats in group M had lower incidences of emesis (M: 4% vs C: 40%), retching (M: 8% vs C: 40%) and lip-licking (M: 30% vs C: 52%) (all P <0.05). The incidence of sialorrhea was not different between groups (M: 21% vs C: 22%). Conclusions and relevance Maropitant 8 mg total PO was effective in reducing morphine and dexmedetomidine-induced emesis by 10-fold, when administered as early as 18 h in advance to healthy cats. Maropitant PO could be useful for administration the evening prior to a scheduled procedure requiring sedation/anesthesia to decrease the incidence of emesis.