Abstract Recent research has investigated predictors of English Medium Instruction (EMI) academic success in Higher Education in various contexts; however, mixed findings have been reported, and empirical research in emerging contexts like Vietnam is relatively scarce. In addition, little is known about the associations between tertiary EMI outcome, gender, and high school performance. To fill these research gaps, the present study was conducted to explore the roles of gender, high school grades, English language proficiency and vocabulary knowledge (both receptive and productive knowledge) in Vietnamese tertiary EMI academic achievement. To this end, 78 Vietnamese undergraduates majoring in business studies participated in the study. The participants took the Vocabulary Levels Test (Schmitt et al. 2001) and Productive Vocabulary Levels Test (Laufer and Nation 1999) to measure their receptive and productive vocabulary knowledge. Their English language proficiency test scores, EMI course grades, and high school grade point average (GPA) were also collected for data analysis. Simple linear regression analyses revealed that high school GPA, English language proficiency together with both receptive and productive vocabulary knowledge significantly predicted EMI academic outcome while gender did not. The results are discussed with implications for EMI in Higher Education.