OBJECTIVES: To identify the clinical, ethnic, and genetic factors contributing to the varying risks of postoperative nausea and vomiting (PONV) among a Brazilian population undergoing cancer surgery. METHODS: A case-control study was conducted involving 152 patients who experienced vomiting and/or retching (cases) and 158 patients who did not report nausea, vomiting, or retching (controls) within 24 h following oncological surgeries. This study is registered as 'Genetic Polymorphism and postoperative nausea and vomiting (PONV)' under registration number NCT03627780 (https://clinicaltrials.gov/study/NCT03627780). Thirty-two polymorphisms associated with PONV predisposition and 15 polymorphisms for ancestry analysis were genotyped via real-time polymerase chain reaction (PCR) with customised TaqMan low-density array (TLDA) cards. RESULTS: The C allele of the rs208294 polymorphism ( CONCLUSIONS: A previous history of PONV or motion sickness was identified as being the strongest predictor of PONV in our analysis. Genetic association, ancestry and external validation analyses suggest that genetic factors for PONV may significantly differ across populations of different continental origins.